Pituitary Microadenomas Medication

Updated: Nov 07, 2022
  • Author: Andre E Manov, MD, MSHM, FACP, CPE; Chief Editor: George T Griffing, MD  more...
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Medication

Medication Summary

For the most common microadenomas, that is, prolactinomas, administer a dopaminergic drug such as bromocriptine or cabergoline (see Hyperprolactinemia). Cabergoline is preferentially used because in patients with microprolactinomas it leads to normalization of prolactin levels in 83% of patients, compared with 53-70% of patients taking bromocriptine. Also, with cabergoline, restoration of ovulatory cycles and fertility is achieved in 72% of patients with microprolactinomas, compared with 52% of patients taking bromocriptine. Tumor shrinkage and resolution of galactorrhea occur in, respectively, 80% and 86% of patients with microprolactinomas taking cabergoline, while in patients taking bromocriptine, tumor shrinkage is achieved in 60% of patients. [20, 32]

The superior efficacy of cabergoline is related to the drug's higher affinity to D2 receptors on microprolactinomas. Also, cabergoline is preferentially used because of better patient compliance, being taken once or twice a week versus daily or up to three times a day for bromocriptine (this difference being due to cabergoline's longer half-life). In addition, cabergoline has fewer side effects than bromocriptine and so is better tolerated. Moreover, in 70-80% of patients with microprolactinomas who are resistant to bromocriptine, switching to cabergoline leads to normalization of prolactin levels.

For patients with microadenomas that are oversecreting TSH and who present with hyperthyroidism, the use of iSRLs is appropriate before TSS. They normalize FT4/FT3 in 96% of patients and decrease TSH by more than 50%; iSRLs also reduce tumor size in more than half of patients. Sometimes they are used long-term in patients refusing TSS, which is the primary treatment for the disease. Research found that approximately 4% of patients required methimazole or PTU in addition to iSRLs to control their hyperthyroidism before surgery. [53]

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Dopamine agonists

Class Summary

Dopamine agonists directly stimulate dopamine receptors on the lactotrope. The dopaminergic neurons in the tuberoinfundibular process normally inhibit the secretion of prolactin from the anterior pituitary by secreting dopamine. In a study of 827 patients with hyperprolactinemia (81 of whom had macroadenomas), Corenblum found that treatment with bromocriptine normalized hyperprolactinemia in 85%, reversed symptoms in 93%, and reversed hypogonadism in 94%. [64] Similar results are reported with cabergoline, which has less intolerance and resistance. [18]

Bromocriptine (Parlodel)

Bromocriptine is a semisynthetic ergot alkaloid derivative, strong dopamine D2-receptor agonist, and partial dopamine D1-receptor agonist. It inhibits prolactin secretion, with no effect on other pituitary hormones. It may be administered with food to minimize the possibility of gastrointestinal irritation. Bromocriptine is given 1-2 times per day.

Cabergoline (Dostinex)

Cabergoline is a long-acting dopamine receptor agonist with a high affinity for D2 receptors. Prolactin secretion by the anterior pituitary is primarily under hypothalamic inhibitory control exerted through dopamine. Cabergoline is administered 1-2 times per week.

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Somatostatin Analogs

Lanreotide (Somatuline Depot)

Lanreotide depot is long-acting somatostatin analog given to patients with acromegaly who have inadequate response to or cannot be treated with transsphenoidal surgery (TSS) or radiotherapy. The drug is given via deep subcutaneous injection every 4 weeks. It decreases oversecretion of growth hormone in acromegaly. There is, additionally, an autogel form, which is also administered subcutaneously. Lanreotide decreases growth hormone and IGF-1 levels.

Octreotide (Sandostatin LAR, Bynfezia Pen, Mycapssa)

Octreotide depot is a long-acting somatostatin analog for long-term treatment of patients with acromegaly who have an inadequate response to or cannot be treated with surgery and/or radiotherapy. The drug is given by deep subcutaneous injection every 4 weeks. It may sometimes be used in conjunction with radiotherapy, because of the delayed effect of radiation treatment. It reduces the oversecretion of growth hormone in acromegaly, decreasing growth hormone and IGF-1 levels.

Pasireotide (Signifor, Signifor LAR)

Pasireotide long-acting release (LAR) is a long-acting somatostatin analog for long-term treatment of patients with Cushing disease or acromegaly who have an inadequate response to or cannot be treated with surgery and/or radiotherapy. The drug must be given intramuscularly by a trained health-care specialist every 4 weeks. It may sometimes be used in conjunction with radiotherapy, because of the delayed effect of radiation treatment. The drug decreases growth hormone oversecretion and IGF-1 in acromegaly and the oversecretion of ACTH in Cushing disease.

There is a short-acting form of the drug used in the treatment of Cushing disease, that is administered twice daily subcutaneously.

Octreotide (Mycapssa, Bynfezia Pen, Sandostatin)

Mycapssa is an oral octreotide administered as a delayed-released capsule. It is a somatostatin analog for the treatment of acromegaly that is resistant to TSS or radiotherapy, for use in patients who refuse both treatments, or for administration when TSS for acromegaly is contraindicated. It is administered (with a glass of water) on an empty stomach at least 1 hour before or 2 hours after a meal. Its effect is comparable to that of iSRLs for the treatment of acromegaly. It decreases growth hormone and IGF-1 levels.

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Metabolic & Endocrine, Other

Pegvisomant (Somavert)

Pegvisomant is a highly selective growth hormone receptor antagonist that is used to treat acromegaly. The drug blocks hepatic production of IGF-1 under the influence of growth hormone. It is given subcutaneously once daily, with titration based on IGF-1 level. The drug is used in patients who have recurrent disease after TSS for acromegaly or who refuse surgical/radiation treatment for acromegaly; it is also sometimes given with iSRLs to control the disease.

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Selective Estrogen Receptor Modulators

Clomiphene (Clomid, Serophene)

This drug is used in patients with acromegaly accompanied by hypogonadism who have had an inadequate response to or cannot be treated with surgery and/or radiotherapy, as an add-on therapy to somatostatin analogs and dopamine agonists. The dose used is 50 mg PO daily. Clomiphene decreases growth hormone–mediated IGF-1 production by the liver.

Raloxifene (Evista)

This drug is used in patients with acromegaly who have had an inadequate response to or cannot be treated with surgery and/or radiotherapy. The dose used is 60 mg twice daily PO. However, raloxifene is used only rarely for the treatment of acromegaly. It decreases IGF-1 production by the liver resulting from oversecretion of growth hormone.

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Antifungals, Systemic

Ketoconazole (Nizoral)

Ketoconazole is used for the medical management of Cushing disease. It discourages the first step in cortisol synthesis by inhibiting 11-beta-hydroxylase. The daily dose is usually 600-800 mg PO.

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Diagnostics, Endocrine

Metyrapone (Metopirone)

Metyrapone treats Cushing disease by inhibiting the production of adrenal steroids. It inhibits 11-beta-hydroxylase, the enzyme required for synthesis of cortisol from 11-deoxycortisol. It also inhibits aldosterone synthase, the enzyme required for synthesis of aldosterone from 11-deoxycorticosterone. The dose varies between 0.5-6 g per day. It is usually given to patients who are resistant to or refuse TSS and in those patients who are resistant to or refuse radiotherapy.  

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Steroidogenesis Inhibitors

Osilodrostat

Osilodrostat treats Cushing disease by inhibiting the production of adrenal steroids. It inhibits 11-beta-hydroxylase, the enzyme required for the synthesis of cortisol from 11-deoxycortisol. It also inhibits aldosterone synthase, the enzyme required for the synthesis of aldosterone from 11-deoxycorticosterone. To a lesser degree, it inhibits a proximal step in steroidogenesis. It is usually given to patients who are resistant to or refuse TSS and to patients who are resistant to or refuse radiotherapy. The dose is 2-7 g tablets given twice daily.

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Antithyroid Agents

Methimazole (Northyx, Tapazole)

Methimazole is used, albeit rarely, in patients with TSH-producing microadenomas and central hyperthyroidism, in those who refuse TSS and who remain hyperthyroid despite the use of iSRLs, and, together with iSRLs, in patients with central hyperthyroidism (in order to achieve euthyroidism before TSS).

Propylthiouracil (PropylThyracil, PTU)

Propylthiouracil is used, albeit rarely, in patients with TSH-producing microadenomas and central hyperthyroidism, in patients who refuse TSS and who remain hyperthyroid despite the use of iSRLs, or, together with iSRLs, in patients with central hyperthyroidism (in order to achieve euthyroidism before TSS).

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