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Year : 2020  |  Volume : 68  |  Issue : 7  |  Page : 20--27

Current Status of Diagnosis and Management of Functioning Pituitary Tumors: Part II

Jugal V Gada, Prudwiraj Sanamandra, Sagar A Barasara, Yash V Chauhan, Nikhil M Bhagwat 
 Department of Endocrinology, Topiwala National Medical College and BYL Nair Charitable Hospital, Mumbai, Maharashtra, India

Correspondence Address:
Dr. Nikhil M Bhagwat
Department of Endocrinology, Topiwala National Medical College and BYL Nair Charitable Hospital, Dr. A L Nair Road, Mumbai - 400 008, Maharashtra


Functioning pituitary tumors contribute to significant morbidity and mortality. Proper diagnostic approach and management is essential for optimal outcomes. Prolactinomas, the commonest of these, are the only tumors which can be managed medically. Acromegaly, apart from acral enlargement, can have multiple comorbidities like diabetes, hypertension, and obstructive sleep apnea. The primary treatment is surgical and it can be supplemented by radiotherapy and medications such as somatostatin analogs, growth hormone receptor blockers, or cabergoline. Thyrotropin-secreting tumors are rare and present with hyperthyroidism. Optimal preoperative management followed by surgical resection often leads to cure.

How to cite this article:
Gada JV, Sanamandra P, Barasara SA, Chauhan YV, Bhagwat NM. Current Status of Diagnosis and Management of Functioning Pituitary Tumors: Part II.Neurol India 2020;68:20-27

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Gada JV, Sanamandra P, Barasara SA, Chauhan YV, Bhagwat NM. Current Status of Diagnosis and Management of Functioning Pituitary Tumors: Part II. Neurol India [serial online] 2020 [cited 2022 May 20 ];68:20-27
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Full Text

Pituitary tumors are slow-growing benign tumors arising from the anterior pituitary. The anterior pituitary has five cell lines, namely, corticotropes, somatotrophs, thyrotropes, gonadotrophs, and lactotrophs.[1] A tumor arising from any of these cell types causes a distinct clinical syndrome and is called a functional pituitary tumor. Correct approach in diagnosis and treatment may reduce morbidity and mortality caused by the clinical syndrome. In this second part of the review on functioning pituitary tumors, we discuss the presentation and management of growth hormone (GH), prolactin, and thyrotropin-secreting tumors.

Initial workup

A complete pituitary profile should include a thyroid profile, 8 am cortisol (fasting), adrenocorticopic hormone (ACTH), IGF-1, Growth Hormone, Prolactin, follicle-stimulating hormone (FSH), luteinizing hormone (LH) and a and total testosterone in males, whereas a detailed menstrual history in females would give a clue to hypogonadism.[2],[3]

Perimetry is indicated in patients with visual complaints or those with macroadenomas (>1 cm) that extend to the chiasm.[2]

Imaging-Pituitary tumors are best diagnosed by dedicated high-resolution magnetic resonance imaging (MRI) of the hypothalamic-pituitary area in coronal and sagittal planes before and after gadolinium administration with a slice thickness <3 mm and dynamic sequences to obtain preferably cuts of 1 mm.[3],[4]

Perioperative management

Perioperative steroid cover

Preoperative 8 am cortisol levels <3.6 μg/dL are suggestive of ACTH insufficiency and require perioperative steroid cover. Levels between 3.6 and 10 μg/dL require provocative testing with insulin tolerance test (ITT) or short synacthen test. However, synacthen is not freely available in India and ITT is seldom performed and, hence, these patients require stress cover. Patients with cortisol levels >10–15 μg/dL are usually ACTH sufficient. In this group of patients, if selective adenomectomy can be performed, many centers do not prefer perioperative steroid cover and reevaluate the hypothalamic-pituitary-adrenal (HPA) axis at day 1–3 postoperatively with 8 am cortisol levels. However, if selective adenomectomy is not possible, perioperative steroid cover is given. Perioperative steroid cover consists of 48 h of supraphysiological glucocorticoid therapy at tapering doses (50 mg q8h hydrocortisone on day 0, 25 mg q8h on day 1, and 25 mg at 8 am on day 2) with postoperative HPA axis evaluation at day 3–5. Postoperative cortisol levels <3.6 μg/dL require lifelong glucocorticoid replacement. Glucagon stimulation testing is required for levels between 3.6 and 9 μg/dL, levels between 9 and 16 μg/dL require only stress cover, and levels >16 μg/dL are usually cortisol sufficient.[5] In our center, a resource-limited setting, in order to reduce the morbidity and mortality, we prefer to give perioperative glucocorticoid cover to all patients undergoing pituitary surgery.

Diabetes insipidus and syndrome of inappropriate antidiuretic hormone

Electrolyte imbalances following pituitary surgery require close monitoring of fluid intake, urine output, serial serum and urine electrolytes, and osmolality.

Diabetes insipidus (DI) may occur in up to 25% of patients postoperatively. Patients typically complain of polydipsia and polyuria due to an inability to concentrate urine. DI is defined as urine output >3 L/day or 4 mL/kg/h with urine osmolality <300 mOsm/kg in the presence of a normal or elevated serum sodium. DI may be transient, permanent (if the stalk is damaged), or may show a triphasic response.[2],[6],[8]

DI can be managed acutely with either intravenous or subcutaneous desmopressin (0.5–2 μg q24h as required) or subcutaneous vasopressin (5–10 units, duration of action 2–8 h) and repeat dose once urine output increases.[8],[9] Chronic management includes DDAVP—oral (0.1/0.2 mg tablets) or intranasal (10 μg metered dose, to be used only after nasal mucosal healing). Start with lowest dose (0.05 mg) at bedtime and increase the dose and frequency (0.9 mg/day) to avoid polyuria and polydipsia.

Overtreatment increases the risk of hyponatremia.[8] Hence, the patients should be instructed only to drink to thirst and their DI medications be reassessed periodically. Adipsic or comatose patients are managed by balancing fluid intake and desmopressin, with close monitoring of biochemical parameters.[10]

Syndrome of inappropriate antidiuretic hormone (SIADH) can occur in up to 19% patients postoperatively.[11] Mild hyponatremia may be managed as outpatient with fluid restriction, but more severe (<125 mEq/L) requires aggressive inpatient management with fluid restriction, hypertonic saline, and vaptans.[8]

Management of postoperative hypopituitarism

Management of postoperative hypopituitarism is highlighted in [Table 1].[5],[7],[8],[12],[13],[14],[15]{Table 1}


Prolactinomas are pituitary tumors which arise from lactotrophs and account for ~40% of all pituitary tumors.[16] Majority of prolactinomas are microadenomas (<1 cm in diameter) and are 10 times more common in women as they are symptomatic. Macroadenomas (>1 cm in diameter) are common in men. Giant prolactinomas (>4 cm in diameter) are rare.[17],[18]

Premenopausal women commonly present with menstrual disturbances (oligomenorrhea/amenorrhea), galactorrhea, or infertility. Postmenopausal women and most men present with symptoms of mass effect.[19] Several affected men also manifest decreased libido, erectile dysfunction, oligospermia, infertility, and rarely gynecomastia and/or galactorrhea. Low bone mineral density may be observed in both men and women with hypogonadism due to prolactinoma.[3]

The measurement of serum prolactin in a single sample is sufficient for the diagnosis of hyperprolactinemia. Moderate elevations in serum prolactin levels (up to 150 ng/mL) are seen in multiple physiologic and pathologic conditions or due to a wide variety of medications [Table 2] which should be excluded before considering pituitary imaging.{Table 2}

An approach to hyperprolactinemia is shown in [Figure 1].[1],[20],[21],[22],[23],[24]{Figure 1}

Pituitary imaging

Diagnosis of prolactinoma is made when there is sustained hyperprolactinemia with radiologic evidence of a pituitary tumor. A dynamic contrast-enhanced pituitary MRI should be performed to rule out a tumor.[20] However, one should remember that a normal MRI does not exclude the diagnosis of microprolactinoma and that ~10% normal population may harbor pituitary incidentaloma. Primary hypothyroidism is associated with elevated serum prolactin levels. The MRI in such patients may reveal a hyperplastic pituitary which is often misdiagnosed as a prolactinoma.


The goals of treatment are to restore gonadal function by normalizing the serum prolactin levels, relieving mass effects, correcting other pituitary hormone deficiencies, and addressing bone health.

Dopamine agonists (DA) are the first line of management in the treatment of prolactinomas. Cabergoline is preferred over bromocriptine as it is more efficacious in lowering prolactin levels, shrinkage of tumor size, and restoring gonadal function. Medical management of prolactinomas is outlined in [Table 3].[25],[26],[27],[28],[29],[30]{Table 3}

Other considerations

The fall in serum prolactin level typically occurs within the first 2–3 weeks, whereas a decrease in tumor size usually occurs by 6 weeks of treatment initiation.[31] Giant prolactinomas and patients with visual impairment at baseline can also be managed successfully with DAs.[32]

High-dose cabergoline use in Parkinson's disease patients is associated with valvular heart disease but not with the lower doses used in prolactinoma.[33],[34] Echocardiography may not be required as the risk for cardiac valvular regurgitation is low at the doses used.[20]

CSF rhinorrhea may occur after starting DA if tumors which invade the sellar floor or extend into the sphenoid sinus or ethmoidal sinus.[35]

Resistance to therapy is defined by a failure to achieve a normal prolactin level and a failure to achieve a 50% reduction in tumor size with maximal conventional doses of DA (≥15 mg/day of bromocriptine or 2 mg/week of cabergoline for at least 3 months).[36],[37],[38] Mechanism of resistance, although poorly understood, is due to decreased expression of D2 receptors.[37] 25% tumors may be resistant to bromocriptine, of which 80% may respond when switched to cabergoline.[29] 10% tumors may be resistant to cabergoline,[27] in which cases, increasing the doses up to 11–12 mg/week may help.[27]

Monitoring[20] includes periodic prolactin estimations and therapy is titrated to normalize prolactin levels and reverse the hypogonadism. MRI should be done at 1 year, or at 3 months in macroadenoma if they have a poor response to therapy or if new symptoms occur. Visual fields (in case of chiasmal involvement) and bone mineral density should be regularly monitored.

DA therapy may be tapered after at least 2 years of therapy in patients who maintain a normal prolactin concentration and have no remnant tumor on MRI.[20]

Surgical indications are:[39]

Increasing tumor size or persistent chiasmal compression despite optimal medical therapyPituitary apoplexyIntolerant or resistance to DA therapyIn women seeking fertility, if DA-resistant microadenoma or a macroadenoma near chiasm (with prepregnancy debulking)Medically unresponsive cystic prolactinomaCSF leak during administration of DAMacroadenoma in a psychiatric patient with contraindication to DA.

The remission rate after TSS in prolactinoma patients is variable (30%–93%). Restarting DAs in resistant prolactinomas after debulking surgery normalizes prolactin levels in half the patients and with lower doses.[40]

Resistant (failure of medical and/or surgical therapy) or malignant prolactinomas may be subjected to radiotherapy, although it may take up to 20 years for maximal effect with a response rate ranging from 26%–31.4% depending upon modality of radiotherapy.[36],[41]

Temozolomide therapy may be considered for malignant prolactinomas.[20]


Acromegaly is caused by proliferation of somatotrophs resulting in hypersecretion of GH.[42] It has an incidence of ~10 per million population, and the prevalence of 28–137 per million.


The most common cause is GH secreting pituitary tumor (98%). Macroadenomas are common. Ectopic secretion of growth hormone-releasing hormone (GHRH) [hypothalamic or peripheral tumor] or GH and genetic causes (X-linked acrogigantism, MEN-1 syndrome, Carney Complex, McCune-Albright syndrome, and AIP mutation) are rare causes.[42]

Clinical features

Acromegaly has insidious onset and is a slowly progressive disease. GH/IGF-1 hypersecretion characteristic clinical features of acromegaly include acral and soft tissue enlargement leading to large hands, large fleshy nose, coarsening of facial features, musculoskeletal manifestations, hyperhidrosis, and deepening of the voice. These, however, are the presenting features in only ~20% of patients.[43] The common (>80%) presentations include headache, impaired vision due to optic chiasm compression, or other symptoms related to mass effect. Obstructive sleep apnea and metabolic disturbances (diabetes mellitus) are common in acromegaly patients. Acromegalics have an increased risk of colonic polyp.[44],[45]

Associated cardiac conditions include hypertension, left ventricular dysfunction, valvular regurgitation, and asymmetric septal hypertrophy. The overall mortality rate is higher in acromegaly patients with a standardized mortality ratio of ~1.72. Deaths attributed to acromegaly are mainly due to cardiovascular, respiratory, and cerebrovascular diseases.


Serum IGF-1 level is the initial screening method of choice. Hepatic and renal failure, malnutrition, severe infection, poorly controlled diabetes mellitus, and hypothyroidism can result in falsely low levels. The diagnosis is confirmed by unsuppressed nadir GH (GH >1 ng/mL; standard assay, GH >0.4 ng/mL; sensitive assay) level after 75 g OGTT with documented hyperglycemia.[46]

MRI is to be done for tumor localization and to assess the parasellar extent.[46] Approximately, 77% of acromegaly patients harbor a macroadenoma,[47] but contrast-enhanced pituitary MRI with two-millimeter slices is recommended to diagnose microadenomas.[46] Densely granulated somatostatinomas appear hypointense while sparsely granulated tumors appear hyperintense on T2W-images.[48]

Preoperatively assessment of prolactin (stalk compression or cosecretion), other pituitary hormones, perimetry, blood glucose, echocardiography, sleep study for OSA, colonoscopy should be done to screen for comorbidities.


Preoperative medical therapy

Routine use of preoperative medical therapy is not indicated but may be considered in patient with increased pharyngeal thickness (can cause difficult intubation), sleep apnea, high output cardiac failure, and uncontrolled diabetes and hypertension.[46],[49],[50]


Transsphenoidal surgery is the first line of treatment for a pituitary tumor. The cure rate is 73% for microadenomas and 61% for macroadenomas. Small tumor volume, lower Knosp score, lower preoperative GH and IGF-1 level, and experience of surgeon are favorable factors for the remission.[46],[51] Surgical debulking should be considered in patient with parasellar disease to improve subsequent response to medical therapy.[46],[51]

Criteria for cure

Random GH may be assessed immediately post surgery. Normal IGF-1, random GH level less than 1 ng/mL, or nadir GH <1 ng/mL standard assay (<0.4 ng/mL-ultrasensitive assay) after OGTT, done at 12-week post surgery, are defined as cure. Same GH and IGF-1 assay should be used throughout the management.[52] MRI pituitary should be done 12 weeks after surgery.[49]

Management of persistent disease

Resurgery may be considered when there is an accessible intrasellar component.[53]

Medical Therapy: Medical options for acromegaly are shown in [Table 4] Anticonvulsants: opiates, benzodiazepines.[54],[55],[56],[57],[58],[59],[60],[61],[62]{Table 4}


When surgery is not possible or is refusedUncured status after surgeryUsed as a bridge therapy while awaiting the response to radiation therapy.

Combination therapy

When response is partial after high dose of somatostatin receptor ligands (SRL), the addition of pegvisomant results in normalization of IGF-1 in 95% but transient transaminase elevation occurs in 27% patients.[63] Cabergoline combined with SRL normalized IGF-1 levels in 42%–60% patients.[62]


Radiotherapy is considered as an adjuvant therapy in persistent disease or in those who cannot afford medical therapy. Therapeutic effect of stereotactic radiation therapy may take years (mean 3.17 year) and remission rate is 59% at 10 years.[64]

Management of comorbidities

Longitudinal monitoring and treatment of comorbidities like diabetes, hypertension, cardiovascular disease, obstructive sleep apnea, and osteoarthritis should be done. Colonoscopy for colonic polyp screening should be done. These comorbidities may be debilitating in spite of remission.

 TSH-Secreting Tumors

Thyrotropin-secreting tumors (TSH-omas) are a rare cause of hyperthyroidism and comprise 1%–3% of all pituitary tumors.[65],[66]

These patients have a goiter and present with mild symptoms of thyrotoxicosis.[67] These tumors may be large, invasive, and fibrous at the time of resection.[66],[68]

When to suspect?

Inappropriately normal or elevated TSH with elevated serum T4/free T4 levels in a hyperthyroid patient.[69] Most TSH-secreting tumors only secrete TSH; however, cosecretion of prolactin or GH may occur.

Differential diagnosis

Patients with resistance to thyroid hormone, an autosomal dominant inherited disorder, also present with the same thyroid profile and 20% may show a tumor on MRI.[70],[71]


Somatostatin analogs (SSA) with antithyroid drugs (ATD) (carbimazole or methimazole) along with propranolol should be administered in order to restore euthyroidism before surgery to avoid the risk of thyroid storm.[65],[72] Long-term ATD therapy or thyroid ablation without SSAs should be avoided because of concerns of pituitary tumor growth.

Transsphenoidal surgery is the mainstay of therapy. Majority of patients with a microadenoma and 60% with macroadenoma achieve complete cure.[65]

If not cured, medical management, radiotherapy, or repeat surgery may be considered.

Postoperative adjunctive medical therapy with SSA and/or radiation therapy may be useful if there is persistent central hyperthyroidism, especially for nonresectable TSH-omas.[73]

Long-acting SSAs (Octreotide LAR 20 mg 4 weekly) reduce TSH and restore euthyroidism in 90% patients, reduce goiter size in 30% patients, reduce tumor size in 40% patients, and visual improvement occurs in 70% patients.[65],[67],[73]

Criteria for cure

Remission of hyperthyroidism, disappearance of neurological symptoms, negative imaging, and normalization of thyroid function tests including the molar ratio criteria for cure. Undetectable TSH levels 1 week after surgery indicate complete adenomectomy.[74]


The management of functional pituitary tumors is a team approach. There has to be a dialog between the endocrinologist and neurosurgeon for proper management and optimizing outcomes.[75],[76],[77],[78]

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.


1Kaiser UB, Ho KY. Pituitary Physiology and Diagnostic Evaluation. In: Melmed S, Auchus RJ, Goldfine AB, Koenig RJ, Rosen CJ, editors. William's Textbook of Endocrinology. 13th ed. Philadelphia, PA: Elsevier; 2016. p. 177.
2Zada G, Woodmansee W, Iuliano S, Laws E. Perioperative management of patients undergoing transsphenoidal pituitary surgery. Asian J Neurosurg 2010;5:1-6.
3Kleinberg D, Melmed S. Pituitary Masses and Tumours. In: Melmed S, Auchus RJ, Goldfine AB, Koenig RJ, Rosen CJ, editors. William's Textbook of Endocrinology. 13th ed. Philadelphia, PA: Elsevier; 2016. p. 232-99.
4Wolpert SM, Molitch ME, Goldman JA, Wood JB. Size, shape, and appearance of the normal female pituitary gland. AJR Am J Roentgenol 1984;143:377-81.
5Inder WJ, Hunt PJ. Glucocorticoid replacement in pituitary surgery: Guidelines for perioperative assessment and management. J Clin Endocrinol Metab 2002;87:2745-50.
6Woodmansee WW, Carmichael J, Kelly D, Katznelson L. AACE/ACE Disease State Clinical Review: Postoperative Management Following Pituitary Surgery. Endocr Pract. 2015;21:832-8.
7Fleseriu M, Hashim IA, Karavitaki N, Melmed S, Murad MH, Salvatori R, et al. Hormonal replacement in hypopituitarism in adults: An endocrine society clinical practice guideline. J Clin Endocrinol Metab 2016;101:3888-921.
8Prete A, Corsello SM, Salvatori R. Current best practice in the management of patients after pituitary surgery. Ther Adv Endocrinol Metab 2017;8:33-48.
9Murphy-Human T, Diringer MN. Sodium disturbances commonly encountered in the neurologic intensive care unit. J Pharm Pract 2010;23:470-82.
10Robinson A, Verbalis JG. Posterior Pituitary. In: Melmed S, Auchus RJ, Goldfine AB, Koenig RJ, Rosen CJ, editors. William's Textbook of Endocrinology. 13th ed. Philadelphia, PA: Elsevier; 2016. p. 300-32.
11Jahangiri A, Wagner J, Tran MT, Miller LM, Tom MW, Kunwar S, et al. Factors predicting postoperative hyponatremia and efficacy of hyponatremia management strategies after more than 1000 pituitary operations: Clinical article. J Neurosurg 2013;119:1478-83.
12Slawik M, Klawitter B, Meiser E, Schories M, Zwermann O, Borm K, et al. Thyroid hormone replacement for central hypothyroidism: A randomized controlled trial comparing two doses of thyroxine (T4) with a combination of T4 and triiodothyronine. J Clin Endocrinol Metab 2007;92:4115-22.
13Molitch ME, Clemmons DR, Malozowski S, Merriam GR, Vance ML. Evaluation and treatment of adult growth hormone deficiency: An endocrine society clinical practice guideline. J Clin Endocrinol Metabol 2011;96:1587-609.
14Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, et al. Testosterone therapy in men with androgen deficiency syndromes: An endocrine society clinical practice guideline. J Clin Endocrinol Metabol 2010;95:2536-59.
15Stuenkel CA, Davis SR, Gompel A, Lumsden MA, Murad MH, Pinkerton JV, et al. Treatment of symptoms of the menopause: An endocrine society clinical practice guideline. J Clin Endocrinol Metab 2015;100:3975-4011.
16Colao A. The prolactinoma. Best Pract Res Clin Endocrinol Metabol 2009;23:575-96.
17Ciccarelli A, Daly AF, Beckers A. The epidemiology of prolactinomas. Pituitary 2005;8:3-6.
18Murphy FY, Vesely DL, Jordan RM, Flanigan S, Kohler PO. Giant invasive prolactinomas. Am J Med 1987;83:995-1002.
19Khare S, Lila AR, Patt H, Yerawar C, Goroshi M, Bandgar T, et al. Gender differences in macroprolactinomas: A single centre experience. Endocr Connect 2016;5:20-7.
20Melmed S, Casanueva FF, Hoffman AR, Kleinberg DL, Montori VM, Schlechte JA, et al. Diagnosis and treatment of hyperprolactinemia: An endocrine society clinical practice guideline. J Clin Endocrinol Metab 2011;96:273-88.
21Chahal J, Schlechte J. Hyperprolactinemia. Pituitary 2008;11:141-6.
22Glezer A, Soares CRJ, Vieira JG, Giannella-Neto D, Ribela MTCP, Goffin V, et al. Human macroprolactin displays low biological activity via its homologous receptor in a new sensitive bioassay. J Clin Endocrinol Metab 2006;91:1048-55.
23Barkan AL, Chandler WF. Giant pituitary prolactinoma with falsely low serum prolactin: The pitfall of the “high-dose hook effect”: Case report. Neurosurgery 1998;42:913-6.
24Robinson A, Verbalis JG. Posterior Pituitary. In: Melmed S, Auchus RJ, Goldfine AB, Koenig RJ, Rosen CJ, editors. William's Textbook of Endocrinology. 13th ed. Philadelphia, PA: Elsevier; 2016. p. 300-32.
25Berinder K, Stackenäs I, Akre O, Hirschberg AL, Hulting AL. Hyperprolactinaemia in 271 women: Up to three decades of clinical follow-up. Clin Endocrinol 2005;63:450-5.
26Wang AT, Mullan RJ, Lane MA, Hazem A, Prasad C, Gathaiya NW, et al. Treatment of hyperprolactinemia: A systematic review and meta-analysis. Syst Rev 2012;1:33.
27Ono M, Miki N, Kawamata T, Makino R, Amano K, Seki T, et al. Prospective study of high-dose cabergoline treatment of prolactinomas in 150 patients. J Clin Endocrinol Metab 2008;93:4721-7.
28Webster J, Piscitelli G, Polli A, D'Alberton A, Faisetti L, Ferrari C, et al. Dose-dependent suppression of serum prolactin by cabergoline in hyperprolinaemia: A placebo controlled, double blind, multicentre study. Clin Endocrinol 1992;37:534-41.
29Verhelst J, Abs R, Maiter D, Van Den Bruel A, Vandeweghe M, Velkeniers B, et al. Cabergoline in the treatment of hyperprolactinemia: A study in 455 patients. J Clin Endocrinol Metab 1999;84:2518-22.
30Colao A, Di Sarno A, Landi ML, Scavuzzo F, Cappabianca P, Pivonello R, et al. Macroprolactinoma shrinkage during cabergoline treatment is greater in naive patients than in patients pretreated with other dopamine agonists: A prospective study in 110 patients 1. J Clin Endocrinol Metab 2000;85:2247-52.
31Webster J, Piscitelli G, Polli A, Ferrari CI, Ismail I, Scanlon MF. A comparison of cabergoline and bromocriptine in the treatment of hyperprolactinemic amenorrhea. N Engl J Med 1994;331:904-9.
32Acharya SV, Gopal RA, Menon PS, Bandgar TR, Shah NS. Giant prolactinoma and effectiveness of medical management. Endocr Pract 2010;16:42-6.
33Khare S, Lila AR, Patil R, Phadke M, Kerkar P, Bandgar T, et al. Long-term cardiac (valvulopathy) safety of cabergoline in prolactinoma. Indian J Endocrinol Metab 2017;21:154-9.
34Wakil A, Rigby AS, Clark AL, Kallvikbacka-Bennett A, Atkin SL. Low dose cabergoline for hyperprolactinaemia is not associated with clinically significant valvular heart disease. Eur J Endocrinol 2008;159:R11-4.
35Lam G, Mehta V, Zada G. Spontaneous and medically induced cerebrospinal fluid leakage in the setting of pituitary adenomas: Review of the literature. Neurosurg Focus 2012;32:E2.
36Gillam MP, Molitch ME, Lombardi G, Colao A. Advances in the treatment of prolactinomas. Endocr Rev 2006;27:485-534.
37Molitch ME. Management of medically refractory prolactinoma. J Neurooncol 2014;117:421-8.
38Gonzaga M de F de M, de Castro LF, Naves LA, Mendonça JL, Oton de Lima B, Kessler I, et al. Prolactinomas resistant to treatment with dopamine agonists: Long-term follow-up of six cases. Front Endoc (Lausanne) 2018;9:625.
39Klibanski A. Prolactinomas. N Engl J Med 2010;362:1219-26.
40Primeau V, Raftopoulos C, Maiter D. Outcomes of transsphenoidal surgery in prolactinomas: Improvement of hormonal control in dopamine agonist-resistant patients. Eur J Endocrinol 2012;166:779-86.
41Brada M, Jankowska P. Radiotherapy for pituitary adenomas. Endocrinol Metab Clin North Am 2008;37:263-75.
42Melmed S. Medical progress: Acromegaly. N Engl J Med 2006;355:2558-73.
43Reid TJ, Post KD, Bruce JN, Nabi Kanibir M, Reyes-Vidal CM, Freda PU. Features at diagnosis of 324 patients with acromegaly did not change from 1981 to 2006: Acromegaly remains under-recognized and under-diagnosed. Clin Endocrinol 2010;72:203-8.
44Colao A, Ferone D, Marzullo P, Lombardi G. Systemic complications of acromegaly: Epidemiology, pathogenesis, and management. Endocr Rev 2004;25:102-52.
45Rokkas T, Pistiolas D, Sechopoulos P, Margantinis G, Koukoulis G. Risk of colorectal neoplasm in patients with acromegaly: A meta-analysis. World J Gastroenterol 2008;14:3484-9.
46Katznelson L, Laws ER Jr, Melmed S, Molitch ME, Murad MH, Utz A, et al. Acromegaly: An endocrine society clinical practice guideline. J Clin Endocrinol Metab 2014;99:3933-51.
47Giustina A, Chanson P, Bronstein MD, Klibanski A, Lamberts S, Casanueva FF, et al. A consensus on criteria for cure of acromegaly. J Clin Endocrinol Metab 2010;95:3141-8.
48Heck A, Ringstad G, Fougner SL, Casar-Borota O, Nome T, Ramm-Pettersen J, et al. Intensity of pituitary adenoma on T2-weighted magnetic resonance imaging predicts the response to octreotide treatment in newly diagnosed acromegaly. Clin Endocrinol 2012;77:72-8.
49Melmed S, Bronstein MD, Chanson P, Klibanski A, Casanueva FF, Wass JAH, et al. A Consensus Statement on acromegaly therapeutic outcomes. Nat Rev Endocrinol 2018;14:552-61.
50Friedel ME, Johnston DR, Singhal S, Al Khalili K, Farrell CJ, Evans JJ, et al. Airway management and perioperative concerns in acromegaly patients undergoing endoscopic transsphenoidal surgery for pituitary tumors. Otolaryngol Head Neck Surg Off J Am Acad Otolaryngol Neck Surg 2013;149:840-4.
51Buchfelder M, Schlaffer S-M. The surgical treatment of acromegaly. Pituitary 2017;20:76-83.
52Sherlock M, Reulen RC, Aragon-Alonso A, Ayuk J, Clayton RN, Sheppard MC, et al. A paradigm shift in the monitoring of patients with acromegaly: Last available growth hormone may overestimate risk. J Clin Endocrinol Metab 2014;99:478-85.
53Wilson TJ, McKean EL, Barkan AL, Chandler WF, Sullivan SE. Repeat endoscopic transsphenoidal surgery for acromegaly: Remission and complications. Pituitary 2013;16:459-64.
54Murray RD, Melmed S. A critical analysis of clinically available somatostatin analog formulations for therapy of acromegaly. J Clin Endocrinol Metab 2008;93:2957-68.
55Bhayana S, Booth GL, Asa SL, Kovacs K, Ezzat S. The implication of somatotroph adenoma phenotype to somatostatin analog responsiveness in acromegaly. J Clin Endocrinol Metab 2005;90:6290-5.
56Melmed S, Cook D, Schopohl J, Goth MI, Lam KSL, Marek J. Rapid and sustained reduction of serum growth hormone and insulin-like growth factor-1 in patients with acromegaly receiving lanreotide Autogel therapy: A randomized, placebo-controlled, multicenter study with a 52 week open extension. Pituitary 2010;13:18-28.
57Giustina A, Mazziotti G, Torri V, Spinello M, Floriani I, Melmed S. Meta-analysis on the effects of octreotide on tumor mass in acromegaly. PLoS One 2012;7:e36411.
58Bruns C, Lewis I, Briner U, Meno-Tetang G, Weckbecker G. SOM230: A novel somatostatin peptidomimetic with broad somatotropin release inhibiting factor (SRIF) receptor binding and a unique antisecretory profile. Eur J Endocrinol 2002;146:707-16.
59Colao A, Bronstein MD, Freda P, Gu F, Shen CC, Gadelha M, et al. Pasireotide versus octreotide in acromegaly: A head-to-head superiority study. J Clin Endocrinol Metab 2014;99:791-9.
60Trainer PJ, Drake WM, Katznelson L, Freda PU, Herman-Bonert V, van der Lely AJ, et al. Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant. N Engl J Med 2000;342:1171-7.
61van der Lely AJ, Biller BMK, Brue T, Buchfelder M, Ghigo E, Gomez R, et al. Long-term safety of pegvisomant in patients with acromegaly: Comprehensive review of 1288 subjects in ACROSTUDY. J Clin Endocrinol Metab 2012;97:1589-97.
62Sandret L, Maison P, Chanson P. Place of cabergoline in acromegaly: A meta-analysis. J Clin Endocrinol Metab 2011;96:1327-35.
63Neggers S, Herder WW de, Janssen J, Feelders RA, Lely AJ van der. Combined treatment for acromegaly with long-acting somatostatin analogs and pegvisomant: Long-term safety for up to 4.5 years (median 2.2 years) of follow-up in 86 patients. Eur J Endocrinol 2009;160:529-33.
64Ding D, Mehta GU, Patibandla MR, Lee C-C, Liscak R, Kano H, et al. Stereotactic radiosurgery for acromegaly: An international multicenter retrospective cohort study. Neurosurgery 2019;84:717-25.
65Beck-Peccoz P, Lania A, Beckers A, Chatterjee K, Wemeau J-L. 2013 European thyroid association guidelines for the diagnosis and treatment of thyrotropin-secreting pituitary tumors. Eur Thyroid J 2013;2:76-82.
66Nazato DM, Abucham J. Diagnosis and treatment of TSH-secreting adenomas: Review of a longtime experience in a reference center. J Endocrinol Invest 2018;41:447-54.
67Beck-Peccoz P, Lanea A, Persani L. TSH-Producing Adenomas. In: Jameson JL, De Groot L, editors. Endocrinology: Adult and Pediatric. 7th ed. Philadelphia, PA: Elsevier; 2016. p. 266-74.
68Cossu G, Daniel RT, Pierzchala K, Berhouma M, Pitteloud N, Lamine F, et al. Thyrotropin-secreting pituitary adenomas: A systematic review and meta-analysis of postoperative outcomes and management. Pituitary 2019;22:79-88.
69Timmons JG, Mukhopadhyay B. Hyperthyroxinemia with a non-suppressed TSH: How to confidently reach a diagnosis in this clinical conundrum. Hormones 2020;52:427-40.
70Sriphrapradang C, Srichomkwun P, Refetoff S, Mamanasiri S. A Novel thyroid hormone receptor beta gene mutation (G251V) in a Thai patient with resistance to thyroid hormone coexisting with pituitary incidentaloma. Thyroid 2016;26:1804-6.
71Gurnell M, Visser T, Beck-Peccoz P, Chatterjee V. Resistance to thyroid hormone. In: Jameson LJ, DeGroot LJ, editors. Endocrinology, Adult and Pediatric. 7th ed, Vol II. 2015. p. 1648-55.
72Ross DS, Burch HB, Cooper DS, Greenlee MC, Laurberg P, Maia AL, et al. 2016 American Thyroid Association Guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis. Thyroid 2016;26:1343-421.
73Socin HV, Chanson P, Delemer B, Tabarin A, Rohmer V, Mockel J, et al. The changing spectrum of TSH-secreting pituitary adenomas: Diagnosis and management in 43 patients. Eur J Endocrinol 2003;148:433-42.
74Losa M, Giovanelli M, Persani L, Mortini P, Faglia G, Beck-Peccoz P. Criteria of cure and follow-up of central hyperthyroidism due to thyrotropin-secreting pituitary adenomas. J Clin Endocrinol Metab 1996;81:3084-90.
75Jane JA Jr, Laws ER Jr. The management of non-functioning pituitary adenomas. Neurol India 2003;51:461-5.
76Tripathi M, Sanjeev CC, Roy AK. Chasing hyponatraemia: unusual presentation. Neurol India 2001;49:197-9.
77Dutta P, Hajela A, Pathak A, Bhansali A, Radotra BD, Vashishta RK, et al. Clinical profile and outcome of patients with acromegaly according to the 2014 consensus guidelines: Impact of a multidisciplinary team. Neurol India 2015;63:360-8.
78Behari S. Management of prolactinomas: the fine print between the lines. Neurol India 2011;59:501-3.