Thyrotropinoma, or TSHoma, are TSH-secreting tumors that are a subtype of pituitary adenoma. Accounting for less than 1% of all functional pituitary adenomas, TSHomas are a rare cause of hyperthyroidism.1 World Health Organization (WHO) classification, revised in 2022, classifies thyrotroph tumors as PIT1 lineage. Mature TSHomas may become fibrotic but are not typically highly invasive.2
Most TSHomas cause inappropriate secretion of TSH, leading patients to present with the symptoms of hyperthyroidism. Unlike primary hyperthyroidism, where TSH levels are low or undetectable, TSHomas cause central, or secondary, hyperthyroidism. Symptom severity is related to tumor size, and patients with microadenomas (<1 cm) may be asymptomatic or clinically silent.3 While detection of TSHoma at the microadenoma level has improved due to advancements in diagnostic workup, the majority of TSHomas are diagnosed as macroadenomas (>1 cm). Patients with macroadenomas may have symptoms of invasion and compression from the mass to the surrounding area.
In addition to inappropriate secretion of TSH, TSHomas may cause hypersecretion of the pituitary hormones, growth hormone (GH), and prolactin (PL). Associated symptoms may be common.4
TSHoma Diagnosis & Presentation
Those with a TSHoma typically present with signs of hyperthyroidism, particularly signs that are related to pressure, such as vision loss and headaches. The majority of cases of TSHoma present with visual symptoms. Most patients are diagnosed in their 50s and 60s, occurring equally in men and women.1 Clinical manifestations include:
- thyroid nodule
- visual field defects
- menstrual disorders (e.g., amenorrhea)
- thyrotoxicosis: A dangerous condition that is the combination of hyperthyroidism in addition to excessive levels of circulating thyroid hormones. Thyrotoxicosis, or thyroid storm, may be caused by gland destruction or ingestion of excess exogenous thyroid hormone or iodine.1
If there is hypersecretion of the pituitary hormones, GH and PL, the patient may present with a combination of hyperthyroidism and acromegaly. Symptoms of excess GH include fatigue, headaches, hyperhidrosis, peripheral neuropathies, snoring, sexual dysfunction, and arthralgias.5,6
While pituitary adenomas may accidentally be found with CT/MRI that is done for other reasons, TSHoma should be suspected if there are elevated concentrations of FT4 and FT3. along with normal or high TSH levels.4 Diagnosis at an early stage is important so proper treatment can be established. TSHoma diagnosis may be determined by the following workup:
- Labs: TSH levels, FT4 and FT3 levels7
- Thyroid function tests: Highly sensitive thyrotropin assays, elevated alpha subunit TSH ratio, flat or decreased response to TRH, T3 suppression tests7
- Imaging: TSHoma diagnosis requires imaging to confirm the presence of an adenoma. Pituitary lesions visible on MRI may indicate a TSHoma. MRI has high resolution of soft tissue and provides noninvasive and multidirectional imaging. Imaging performed by an MRI can show the shape, size, and invasion of the tumor, as well as its texture. Those factors are beneficial in making operative plans and determining a prognosis. A CT scan may be done when an MRI contraindicated.7 In addition, if an adenoma is large, a CT scan may provide information about its impact on the surrounding bone structure.
Both stimulatory and inhibitory tests should be employed in the differential diagnosis of TSHomas.4 Ultra-sensitive TSH immunometric assays, such as T3 suppression tests and TRH, can help differentiate TSHomas from other syndromes.8 Other considerations include:
- Pituitary resistance to thyroid hormone (RTH) due to THRB gene mutations: Serum TSH levels within the normal range are found more frequently in RTH, while elevated α subunit concentrations or a high α subunit/TSH molar ratio typically is present in patients with TSHomas.9
- Primary vs. central hyperthyroidism: Primary hyperthyroidism must be ruled out.9
- Primary hypothyroidism: May mask symptoms of TSHoma.10
- Familial dysalbuminemic hyperthyroxinemia (FDH): FDH may cause elevated circulating T3 and T4. FDH is a disorder that may be mistaken for hyperthyroidism.11 TSHoma is not typically familial, so establishing a thorough family history during clinical evaluation may help rule out FDH.8
- Chronic lymphocytic thyroiditis: Causes elevated TSH levels.10
- Medical interference: Certain medications or inadequately controlled conditions can lead to elevated levels of TSH. Poor compliance in patients taking levothyroxine for primary hyperthyroidism can lead to elevated TSH levels.6
- Testing errors: Campi and colleagues observed assay interference as the main source of error when performing thyroid function tests.12
- Thyroxine-binding globulin (TBG) deficiency or excess: The vast majority of circulating thyroid hormone is protein-bound, so deficiencies or excess levels of binding proteins are potential causes of altered total thyroid hormone levels. Patients with TBG deficiency present with low T4 levels, elevated T3 uptake, and normal FT4 and TSH. By finding the absence or low levels of serum TBG, the diagnosis of TBG deficiency can be confirmed. Other potential abnormalities include conditions such as hepatitis, pregnancy, or use of certain medications that may increase TBG levels.13
It should be noted that the presence of a pituitary tumor in a patient with inappropriate secretion of TSH, although indicative of TSHoma, is not necessarily diagnostic of TSHoma, as pituitary incidentalomas have been found on MRI in up to 10% of normal subjects.14
Other parameters that can be beneficial in the differential diagnosis are bone turnover markers, such as carboxy-terminal telopeptide of type-I collagen (ICTP).
ICTP may be significantly increased in TSHoma when compared to those with RTH.15 Total cholesterol is also rarely high in TSHoma.
Treatment of TSHoma
With most pituitary adenomas, including TSHomas, surgery is considered first-line treatment.4 Surgery is performed endoscopically with an endonasal approach.16 Selective transsphenoidal resection or subfrontal adenomectomy may completely remove the tumor and restore normal pituitary and thyroid function.
Complete removal of the tumor is achieved in the majority of patients with microadenoma. However, 60% or less of patients with macroadenoma may be cured.4 Patients with macroadenoma may require further treatment as they are at greater risk for recurrence.7 Tumor size, cavernous sinus invasion (CSI), and firm consistency may affect the extent of resection.16 Potential side effects associated with transsphenoidal pituitary surgery include:7
- diabetes insipidus
- cerebrospinal fluid leak and rhinorrhea
- inappropriate ADH secretion
- postoperative psychosis
- local hematoma
- arterial wall damage
- local abscess
- pulmonary embolism
- visual loss
- vascular occlusion
- CNS damage: Oculomotor palsy, hemiparesis, encephalopathy
- nasal septum perforation
Radiation therapy is not a preferred treatment for TSHoma, as surgery and medication treatment have been proven more effective. Radiation therapy should be proposed when patient has not responded to surgery, even if the patient is still euthyroid, as relapse is likely.4 Additionally, radiation therapy may be an option if a patient is resistant to drug therapy and is not a surgery candidate.17 Complications of radiation therapy in TSHoma include long-term hypopituitarism (40% of patients) and secondary neoplasms (1.5% of patients).7
Medication therapy is used to control hyperthyroidism and reduce tumor size in TSHoma.4 The following are different medication options for treating TSHoma:
Octreotide (Brand name: Sandostatin® (conventional) and Sandostatin LAR®(long release)) and lanreotide (Brand name: Somatuline Depot®Injection, Autogel®)4
Indication (Drug-class use)
Somatostatin (SST) analogs are considered first-line medication therapy, and have been effective at reducing TSH secretion and can restore euthyroid state.9 In at least one case, TSHoma was cured with a long-acting somatostatin analog.4 Somatostatin analog treatment helps normalize circulating thyroid hormone levels in more than 90% of patients and reduced goiter size significantly in about 30% of cases.4 Additionally, somatostatin analog treatment induces a significant tumor mass shrinkage in about 40% of patients and vision improvement in about 70% of patients.4 In one case study by Rabbiosi and colleagues, it was concluded that somatostatin analogs are an effective treatment prior to surgery in young patients experiencing puberty.18 They reduce the risk of neurosurgical complications and hypopituitarisms.19
SSTs may also be indicated in palliative care or for patients who were not cured by surgery.
Mechanism of Action
SSTs work by interacting with somatostatin receptors (SSTRs). SSTs inhibit endocrine and exocrine hormone secretion, including growth hormone (GH), prolactin (PRL), thyrotropin (TSH), cholecystokinin (CCK), gastric inhibitory peptide (GIP), gastrin, motilin, neurotensin, secretin, glucagon, insulin, and pancreatic peptides.20
Somatostatin analogs are available in injection and oral form.21-24 The immediate-release injection solution should be given intravenously or subcutaneously, while the long-acting depot injection suspension formulation should only be given intramuscularly.21-23
SSTs undergo extensive hepatic metabolism. Total body clearance ranges from 7 to 10 L/hour in adult patients. The apparent elimination half-life of immediate-release octreotide injection is 1.7 to 1.9 hours, which is significantly greater than somatostatin’s half-life of 1 to 3 minutes. In patients with acromegaly, the half-life is 3.2 to 4.5 hours for all oral doses (20 to 80 mg per day) and elimination is complete approximately 48 hours after the last dose in patients who have achieved steady-state plasma levels. Approximately 32% of a dose is excreted in the urine as an unchanged drug.21
SSTs may induce invasive growth of TSHoma, and long-term use is not recommended. In addition, single doses of octreotide acetate have been shown to inhibit gallbladder contractility and decreased bile secretion in normal volunteers. In clinical trials (primarily patients with acromegaly or psoriasis), the incidence of biliary tract abnormalities was 63%.21 Lanreotide also may cause a reduction in gallbladder motility.22
Adverse Events Profile
- Gastrointestinal (GI) adverse reactions: GI symptoms are common and include diarrhea, abdominal pain, flatulence, nausea, constipation.21 Patients receiving the depot injection reported less diarrhea, abdominal pain, nausea, but more flatulence and constipation as compared to those receiving the subcutaneous injections. Cholelithiasis and biliary sludge frequently develop in patients on chronic therapy.
- Hypoglycemia: Occurred in 1.5% to 4% of patients, and hyperglycemia was noted in 6% to 27% during clinical trials.21
- Cardiovascular: Bradycardia is a common adverse effect in adults. Other cardiovascular effects reported in clinical trials include hypertension, cardiac arrhythmias, and conduction abnormalities.21
- Absorption: Vitamin B12 deficiency may occur in patients receiving octreotide. In addition, octreotide can cause dietary fat malabsorption.21
- Allergic and dermatologic reactions: Reactions reported during adult clinical trials include injection site reaction (pain, tingling, burning, or stinging with redness or swelling at the injection site). Hyperhidrosis, alopecia, rash (unspecified), pruritus, and flushing occasionally occurred. Arthropathy was noted in 8% to 19.2% of adult octreotide injection suspension depot recipients. Joint pain was noted in 1% to 26% of patients, back pain in 6% to 27.3%, musculoskeletal pain in 5% to 15.4%, myalgia in 18.2% or less, osteoarthritis in 11%, generalized pain in 7% or less, and less than 1% had joint effusion or muscle pain. 21
- General: Fatigue or feelings of drowsiness, headache, and dizziness are fairly common adverse effects of octreotide in adults. Weakness or asthenia has been noted in 1% to 22% during various clinical trials of the various dosage forms.21
- Respiratory: Cold symptoms, influenza-like symptoms, naso-pharyngitis, sinusitis, upper respiratory tract infection, and urinary tract infection have been reported during adult clinical trials with octreotide. Octreotide may cause antibody formation, however occurrence of antibody formation with lanreotide was low.21,22
Octreotide is contraindicated in any patient with hypersensitivity or allergy to octreotide or any of the ingredients in the product.
Egregious Drug Interactions
Octreotide suppresses growth hormone secretion, which may decrease the metabolic clearance of drugs metabolized by CYP3A4. A potential for drug-drug interactions exists with medications metabolized by CYP3A4 with a narrow therapeutic index.22
The following medications may interact with lanreotide22:
- Belladonna alkaloids, ergotamine, phenobarbital
- Dextromethorphan, quinidine
- Elexacaftor, tezacaftor, ivacaftor
- Lutetium lu 177 dotatate
- Pimozide, quinidine
Methimazole (Brand Name: Tapazole®)
Indication Management (Drug-class use)
Methimazole is an antithyroid agent used for treating hyperthyroidism.25 In patients with TSHoma, methimazole may be used to manage hyperthyroidism prior to surgery.4
Mechanism of Action
Methimazole affects thyroid hormone production by interfering with the first step of thyroid hormone biosynthesis in the thyroid gland. Methimazole acts as a substrate for thyroid peroxidase, thereby inhibiting the incorporation of iodide into the thyroid hormone precursor thyroglobulin.26 As a result, thyroid hormone biosynthesis is diminished. Methimazole can deplete thyroglobulin by interrupting the oxidation of the iodide ion and iodotyrosyl groups.27 Consequently, circulating thyroid hormone levels are diminished. Meanwhile, methimazole does not alter the action of existing T4 or T3.26
Methimazole is administered orally. The medication is absorbed in the gastrointestinal tract, reaching peak serum concentrations within 1 to 2 hours after administration. However, it usually takes 2 to 4 months of treatment to achieve initial euthyroid status. Response rates are dependent on several pharmacodynamic and patient variables.23
Antithyroid agents should be discontinued at least 3 days prior to treatment with radioiodine (sodium iodide, I-131).28 Theantithyroid agent may be resumed 3 days after the radioiodine treatment.28 Methimazole is contraindicated in patients with a history of allergy or hypersensitivity to the drug.25 Teratogenesis is a serious concern with methimazole if administered during early pregnancy during the period of organogenesis.25 Methimazole crosses the placental membranes and can cause fetal harm when administered in the first trimester of pregnancy.25
Adverse Events Profile
Minor adverse dermatologic reactions associated with methimazole – including rash (unspecified), alopecia, skin hyperpigmentation, urticaria, and pruritus, may occur. Other minor reactions include arthralgia, vasculitis, myalgia,edema, nephrotic syndrome, lymphadenopathy, periarteritis, and sialadenitis.25
Although less frequent, major adverse reactions include drug fever, insulin autoimmune syndrome (which can lead to hypoglycemic coma), inhibition of myelopoiesis (granulocytopenia, agranulocytosis, thrombocytopenia, and aplastic anemia), a lupus-like syndrome, hypoprothrombinemia, hepatitis, and periarteritis. Nephritis occurs in rare cases. After discontinuing the drug, jaundice may appear for several weeks.25 Additionally, post-marketing cases of acute pancreatitis have been reported.25 There have also been reports of a vasculitis that have resulted in severe complications.25
Having hypersensitivity or allergy to the drug or its components is a contraindication for taking methimazole.
Egregious Drug Interactions
Use of the following medications may interact with methimazole25:
- beta-adrenergic blocking agents
- digitalis glycosides
Indication Management (Drug-class use)
Propylthiouracil, or PTU, is an antithyroid agent used for treating hyperthyroidism.29 PTU carries a risk for hepatotoxicity and therefore should be used only in patients who cannot tolerate methimazole and in whom radioiodine therapy or surgery are contraindicated for the treatment of hyperthyroidism.29 It can be administered to pregnant people in their first trimester, but at the smallest effective dosage.29 Also, because of higher protein binding and ionization, PTU is less likely to transfer to the placenta or be distributed into the breastmilk than methimazole.29 Because of this, PTU may be preferred over methimazole when treatment is needed in pregnant or lactating females.29
Mechanism of Action
Propylthiouracil restricts the synthesis of thyroid hormones in the thyroid gland.29 PTU acts as a substrate for thyroid peroxidase, thereby inhibiting the incorporation of iodide into the thyroid hormone precursor thyroglobulin.26 As a result, thyroid hormone biosynthesis is diminished.
Propylthiouracil is administered orally, is quickly absorbed, and thoroughly metabolized.29 Within 24 hours, about 35% of the drug is eliminated in the urine in both intact and conjugated form.29 The drug has a relatively short half-time, about 2 hours, so dosing every 8 hours may be necessary for maintaining effective circulating levels.26 It may also take extended administration periods to reach euthyroid state because the drug works by inhibiting thyroid hormone synthesis.26
With PTU, there are black box warnings for pregnancy and hepatotoxicity.29Antithyroid agents, including PTU, should be discontinued at least 3 to 4 days prior to treatment with radioiodine (sodium iodide, I-131).28 Antithyroid agents may be reintroduced 3 days after the radioiodine treatment.28 Patients should not take PTU if they have a history of hypersensitivity to the drug or its components.29
Minor adverse reactions include dermatologic issues, such as skin rash and urticaria.29 Possible GI effects include nausea, vomiting, epigastric distress.29 Other minor reactions include arthralgia, paresthesias, loss of taste, taste perversion, abnormal loss of hair, myalgia, headache, pruritus, drowsiness, neuritis, edema, vertigo, skin pigmentation, jaundice, sialadenopathy, and lymphadenopathy.29 Less common than the minor adverse reactions, major adverse reactions include liver injury resulting in hepatitis, liver failure, which has led to liver transplantation or death.
Additionally, inhibition of myelopoiesis (agranulocytosis, granulopenia, and thrombocytopenia), aplastic anemia, drug fever, a lupus-like syndrome (including splenomegaly and vasculitis), hepatitis, periarteritis, and hypoprothrombinemia and bleeding have occurred. Nephritis, glomerulonephritis, interstitial pneumonitis, exfoliative dermatitis, and erythema nodosum have also been reported.29
If a patient has previously experienced hypersensitivity to PTU or its components, PTU is contraindicated.
Egregious Drug Interactions
PTU may have serious interactions with the following medications:29
- beta-adrenergic blocking agents
- digitalis glycosides
Brand Names: Hemangeol®, Inderal LA®, Inderal XL®, InnoPran XL®, Inderal®
Indication Management (Drug-class use)
Propranolol belongs to a class of drugs that are non-selective beta blockers/beta-adrenergic receptor antagonists and is used for the management of hyperthyroidism symptoms and thyrotoxicosis prior to TSHoma surgery.30,4 It is typically used as adjunct therapy with SSTs and antithyroid medications.4
Mechanism of Action
Propranolol works by suppressing the peripheral effects of thyroid hormone. Excess thyroid hormone increases sympathetic nervous system sensitivity to catecholamines.31 Propranolol blocks the response to catecholamines at the receptor site and may alleviate the manifestations of thyrotoxicosis.31 In addition, beta blockers improve symptoms associated with hyperthyroidism and thyrotoxicosis, such as palpitations, excessive sweating, tremors, and retraction of the eyelids.31
Propranolol may be administered orally or intravenously.30,31 Propranolol is ex lipophilic and is widely distributed throughout the body.30 Metabolized first in the liver, the majority binds to plasma proteins before reaching systemic circulation.30
An oral dose of immediate-release propranolol is almost fully absorbed after administration. However, due to high first pass metabolism, bioavailability is only about 25%. When taken with foods rich in protein, its bioavailability increases by approximately 50%, but the time to peak concentration, plasma binding, or half-life does not change.30 Peak concentrations of immediate release tablets is 1 to 4 hours.
The distribution half-life of intravenously administered propranolol is 5 to 10 minutes.32 Propranolol injection has an elimination half-life of about 2 to 5.5 hours.31,32
Abruptly stopping propranolol can result in the exacerbation of angina and myocardial infarction.30 If discontinuance of propranolol is planned, gradual reduction of the dosage should occur over at least a few weeks.30 The patient also should be warned not to abruptly stop taking propranolol without guidance from the prescribing clinician. Prescribing providers should be aware that the beta-blockade caused by propranolol can mask symptoms of hyperthyroidism, such as tachycardia.30
Adverse Events Profile
Most adverse effects of propranolol, such as bradycardia and hypotension, are related to its therapeutic effect. Heart failure has been reported.30,31 Paresthesia in the hands, as well as arterial insufficiency (typically the Raynaud type), have also occurred. Other adverse effects of propranolol are as follows:
- CNS effects: Potential adverse CNS effects of propranolol include dizziness, lethargy, fatigue, weakness, catatonia, an acute reversible syndrome characterized by disorientation to time and place, visual impairment, hallucinations, short-term memory impairment, emotional lability (eg, mood swings), slightly clouded sensorium (eg, confusion), vivid dreams (eg, nightmares), decreased performance on neuropsychometrics, and depression manifested by insomnia.30
- GI effects: Gastrointestinal adverse effects reported with propranolol use include nausea, vomiting, diarrhea, constipation, abdominal pain, epigastric distress, mesenteric arterial thrombosis, and ischemic colitis.30
- Endocrine effects: Beta-blockers can prolong or enhance hypoglycemia by interfering with glycogenolysis and can mask signs of hypoglycemia.30,32
- Respiratory effects: bronchospasm has occurred in patients treated with propranolol.30,32
- Other effects: Lupus-like symptoms and systemic lupus erythematosus have been reported with the use of propranolol. Withdrawal symptoms, including headache, diaphoresis, palpitations, sinus tachycardia, tremor, and hypertension have been associated with abruptly discontinuing beta-blockers in hypertensive patients. Gradual tapering and/or prolonged administration of small doses of propranolol prior to complete cessation may prevent these symptoms.30
Propranolol is contraindicated in those who have hypersensitivity or allergy to the medication or its components.30,31 It’s also contraindicated in patients with cardiogenic shock, sinus bradycardia with a greater than first degree block, and bronchial asthma.30
Egregious Drug Interactions
The use of beta-blockers, such as propranolol, has been well studied, and there are reported drug interactions. Caution should be taken when prescribing the following medications:30,31
Antiarrhythmics, digitalis glycosides, calcium channel blockers, ACE inhibitors, alpha blockers, resperine, inotropic agents, isoproterenol and dobutamine, NSAIDs, antidepressants, anesthetic agents, warfarin, neuroleptic drugs, and thyroxine. Alcohol may also interact with propranolol.
The goal of TSHoma treatment is to remove the adenoma and achieve euthyroidism. Early diagnosis of TSHoma improves surgical outcomes.33 Researchers have found that presurgical medical treatment did not significantly change surgical outcome, and macroadenomas had a significantly lower rate of remission.33 They also found that normal TSH and free thyroid hormone levels were observed in 80% of patients at the last visit. Also, TSHomas treated with surgery or radiotherapy maintained euthyroidism over time.33
Successful surgery is determined by an undetectable TSH level approximately 1 week post operation.1 Pituitary function should be evaluated shortly after surgery to provide hormone replacement therapy if necessary.1 Irradiation followed by somatostatin analogue treatment should be considered if there are contraindications to surgery.33 Postoperatively, the disappearance of neurological signs and symptoms is a good prognostic outcome. However, it may occur even if the tumor is not completely removed.4 If surgery is successful, recurrence is rare.33
For follow-up, the patient should be evaluated both clinically and biochemically more frequently in the first year following surgery. According to the European Thyroid Association guidelines, a patient should be seen 2 or 3 times the first year postoperatively and every year after that.4 Pituitary imaging is recommended every 2 or 3 years.4 In the case of increased TSH and thyroid hormone levels or the appearance of clinical symptoms, it should be done immediately.4 Additionally, if macroadenoma persists, there will need to be visual field follow-up to check for visual function impairment.4
In conclusion, TSHomas are rare and can be difficult to diagnose. With differential diagnosis using thyroid function tests, clinical evaluation, and imaging, early TSHoma diagnosis can improve outcomes. The first-line treatment of thyrotropinoma is surgical removal of the adenoma. Perioperative medication management includes somatostatin analogs, antithyroid medications, and non-selective beta-blockers in order to improve thyroid levels and shrink tumor size.
- Beck-Peccoz P, Persani L, Lania A. Thyrotropin-secreting pituitary adenomas. Endotext [Internet]. 2000. Updated Jan. 11, 2019. Accessed September 2022.
- SL, Mete O, Perry A, Osamura RY. Overview of the 2022 WHO Classification of Pituitary Tumors. Endocr Pathol. 2022 Mar;33(1):6-26. doi: 10.1007/s12022-022-09703-7.
- Kirkman MA, Jaunmuktane Z, Brandner S, Khan AA, Powell M, Baldeweg SE. Active and silent thyroid-stimulating hormone-expressing pituitary adenomas: presenting symptoms, treatment, outcomes, and recurrence. World Neurosurg. 2014;82(6):1224-1231. Accessed September 2022. doi:10.1016/j.wneu.2014.03.031
- Beck-Peccoz P, Lania A, Beckers A, Chatterjee K, Wemeau JL. 2013 European Thyroid Association guidelines for the diagnosis and treatment of thyrotropin-secreting pituitary tumors. European Thyroid Journal. 2013 76–82. Accessed September 2022. doi.org/10.1159/000351007
- Lake M, Krook L, Cruz S. Pituitary adenomas: an overview. American Family Physician. 2013. 88(5):319-27. Accessed September 2022.
- Anand N, Ioachimescu A. Principles and Practice of Sleep Medicine. Endocrine Disorders. Chapter 155, 1507-1518. 6th Edition. Accessed September 2022
- Bitar G, MD, Sciscione A, DO. Clinical Overview of Pituitary Adenoma. Elsevier. Released January 1, 2022. Accessed September 27, 2022.
- Beck-Peccoz P, Andrea L, Persani L. (2016) TSH-Producing Adenomas. Endocrinology: Adult and Pediatric. (3rd edition, Chapter 15, pp. 266-274). Accessed September 2022.
- Beck-Peccoz P, Persani L, Mannavola D, Campi I. Pituitary tumors: TSH-secreting adenomas. Best Pract Res Clin Endocrinol Metab. 2009.23(5):597-606. Accessed September 2022. doi:10.1016/j.beem.2009.05.006
- Yap, Y. W., Ball, S., & Qureshi, Z. (2018). Emergence of a latent TSHoma pituitary macroadenoma on a background of primary autoimmune hypothyroidism. Endocrinology, diabetes & metabolism case reports, 2018, 18-0083. https://doi.org/10.1530/EDM-18-0083
- Khoo, S., Lyons, G., Solomon, A., Oddy, S., Halsall, D., Chatterjee, K., & Moran, C. (2020). Familial dysalbuminemic hyperthyroxinemia confounding management of coexistent autoimmune thyroid disease. Endocrinology, diabetes & metabolism case reports. 2020; 19-0161. Accessed September 2022. https://doi.org/10.1530/EDM-19-0161
- Campi I, Covelli D, Moran C, et al. The Differential Diagnosis of Discrepant Thyroid Function Tests: Insistent Pitfalls and Updated Flow-Chart Based on a Long-Standing Experience. Front Endocrinol (Lausanne). 2020;11:432. Accessed September 2022. doi:10.3389/fendo.2020.00432
- Salvatore D, Davies TF, Schlumberger MJ, Hay ID, Larsen PR. Thyroid physiology and diagnostic evaluation of patients with thyroid disorders. In: Melmed S, Polonsky KS, Larsen PR, Kronenberg HM, eds. Williams Textbook of Endocrinology. 13th ed. Philadelphia, PA: Elsevier; 2016:chap 11. Accessed October 5, 2022
- Hall WA, Luciano MG, Doppman JL, Patronas NJ, Oldfield EH. Pituitary magnetic resonance imaging in normal human volunteers: occult adenomas in the general population. Ann Intern Med. 1994;120(10):817-820. Accessed September 2022. doi:10.7326/0003-4819-120-10-199405150-00001
- Persani L, Preziati D, Matthews CH, Sartorio A, Chatterjee VK, Beck-Peccoz P. Serum levels of carboxyterminal cross-linked telopeptide of type I collagen (ICTP) in the differential diagnosis of the syndromes of inappropriate secretion of TSH. Clin Endocrinol (Oxf). 1997.47(2):207-214. Accessed September 2022. doi:10.1046/j.1365-2265.1997.2351057.x
- Sen HE, Ceylan EC, Atayev S, et al. The endoscopic endonasal transsphenoidal approach for thyrotropin-secreting pituitary adenomas: Single-center experience and clinical outcomes of 49 patients. World Neurosurg. 2022. Accessed September 2022. doi:10.1016/j.wneu.2022.09.027
- Richardson TE, Mathis DA, Mickey BE, et al. Clinical Outcome of Silent Subtype III Pituitary Adenomas Diagnosed by Immunohistochemistry. J Neuropathol Exp Neurol 2015. 74:1170–7. Accessed September 2022. doi 10.1097/nen.0000000000000265
- Socin HV, Chanson P, Delemer B, et al. The changing spectrum of TSH-secreting pituitary adenomas: diagnosis and management in 43 patients. Eur J Endocrinol. 2003;148(4):433-442. Accessed September 2022. doi:10.1530/eje.0.1480433
- Rabbiosi S, Peroni E, Tronconi GM, Chiumello G, Losa M, Weber G. Asymptomatic thyrotropin-secreting pituitary macroadenoma in a 13-year-old girl: successful first-line treatment with somatostatin analogs. Thyroid. 2012;22(10):1076-1079. Accessed September 2022. https://doi.org/10.1089/thy.2012.0077
- Günther T, Tulipano G, Dournaud P, et al. International Union of Basic and Clinical Pharmacology. CV. Somatostatin Receptors: Structure, Function, Ligands, and New Nomenclature. Pharmacol Rev. 2018;70(4):763-835. Accessed September 2022. doi:10.1124/pr.117.015388
- Sandostatin LAR (octreotide) [package insert]. East Hanover, NJ: Novartis Pharmaceutical Corporation; 2021 May. Accessed October 5, 2022.
- Somatulin Depot (lanreotide) [package insert]. Signes, France: Ipsen Pharma Biotech; 2018 Dec. Accessed October 5, 2022.
- Sandostatin injection (octreotide acetate) [package insert]. East Hanover, NJ: Novartis Pharmaceutical Corporation; 2021 May. Accessed October 5, 2022.
- Mycapssa (octreotide) [package insert]. Dublin, Ireland: Amryt Pharmaceuticals DAC; 2022. Accessed October 5, 2022.
- Tapazole (methimazole) [package insert]. Wilmington, NC; Manufactured by AAI Pharma for Pfizer; 2015 Dec. Accessed October 5, 2022.
- Tischkau S. Drug Therapy for the Management of Thyroid Disorders. Brody’s Human Pharmacology. 6th ed. Elsevier; 2019:449-454. Accessed October 5, 2022.
- Singh G, Correa R. Methimazole. In: StatPearls. NCBI Bookshelf version. StatPearls Publishing; 2022. Accessed October 5, 2022. https://www.ncbi.nlm.nih.gov/books/NBK545223/
- Meier DA, Brill DR, Becker DV, et al. Procedure guideline for therapy of thyroid disease with (131)iodine. J Nucl Med. 2002;43(6):856-861. Accessed October 5, 2022.
- Propylthiouracil tablets [package insert]. Fort Lee, NJ. DAVAPharmaceuticals.; 2010. Accessed October 5, 2022.
- Inderal LA (propranolol sustained-release) capsules [package insert]. Baudette, MN: ANI Pharmaceuticals, Inc. 2019 Aug. Accessed October 5, 2022.
- Hollenberg A, Wiersinga W. Hyperthyroid Disorders. In: Williams Textbook of Endocrinology. 14th ed. Elsevier; 2020:363-403. Accessed October 5, 2022.
- Propranolol HCl injection [package insert]. Deerfield, IL: Baxter Healthcare Corporation; 2008 Jan. Accessed October 5, 2022.
- Malchiodi E, Profka E, Ferrante E, et al. Thyrotropin-secreting pituitary adenomas: outcome of pituitary surgery and irradiation. J Clin Endocrinol Metab 2014; 99:2069-2076. Accessed 2022. doi:10.1210/jc.2013-4376
Erin Davis, MS, RDN, CDCES, is a freelance medical writer and consultant who has over 15 years of clinical and community experience as a dietitian and diabetes educator. A graduate of Michigan State University and Case Western University, Erin lives on a hobby farm in Michigan with her husband and three children.