McCune-Albright Syndrome Medication

Updated: Jan 05, 2021
  • Author: Gabriel I Uwaifo, MD; Chief Editor: George T Griffing, MD  more...
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Medication Summary

At present, no therapy addresses the underlying molecular problem in McCune-Albright syndrome (MAS) (ie, inappropriate activation of the G protein subunit Gs alpha). Various medications may be administered to correct various endocrine and metabolic derangements, including aromatase inhibitors, hormones, steroids, somatostatin analogues, dopamine agonists, bisphosphonates, estrogen receptor antagonists, antithyroid agents, and metabolic agents.

In a 2014 study, alendronate therapy induced improvement in aBMD and decreased the level of the bone resorption marker NTX-telopeptides but did not effect pain or functional parameters or serum osteocalcin. [67]

Continuous positive effect with long-term safety data was found for zoledronic acid therapy for MAS with severe bone destruction. [68]

Combined therapy with cyproterone acetate, ketoconazole, and leuprolide depot in a boy with concomitant atypical MAS increased predicted adult height. [69]


Aromatase Inhibitors

Class Summary

Aromatase inhibitors are the mainstay of therapy in girls with persistent estradiol elevation. They have also been used in males. With adequate treatment response, serum estrone and estradiol levels are reduced. Patients who respond to treatment should continue therapy until the age of normal puberty or until a bone age of 15-16 years. Among the potential adverse effects associated with medication use are transient abdominal cramping, diarrhea, and mild hepatic inflammation.

Anastrozole (Arimidex)

Anastrozole is a highly selective aromatase inhibitor that significantly lowers serum estradiol concentrations by inhibiting the conversion of adrenally generated androstenedione to estrone. Daily dosing is convenient, and case reports have shown good response; however, larger studies are still needed.

Letrozole (Femara)

Letrozole is a competitive inhibitor of the aromatase enzyme system that leads to a reduction in plasma estrogen levels in postmenopausal women. Although this agent has been used extensively in breast cancer treatment, experience to date in MAS management is limited. Letrozole may decrease pain in patients whose conditions have previously failed other treatments.



Class Summary

Hormones are given to correct endocrine disorders associated with sexual precocity manifestations (98% of cases), such as pubarche, menarche, and thelarche.

Medroxyprogesterone (Provera, Depo-Provera)

Progestins stop endometrial cell proliferation, allowing organized sloughing of cells after withdrawal. Medroxyprogesterone typically does not stop an acute bleeding episode but produces a normal bleeding episode after withdrawal.



Class Summary

Glucocorticoids are used for replacement therapy after adrenalectomy for infantile Cushing syndrome.

Mineralocorticoids are used for replacement therapy after adrenalectomy for infantile Cushing syndrome. They act on fluid and electrolyte balance and enhance sodium reabsorption in the kidney, resulting in expanded extracellular fluid volume. They increase renal excretion of potassium and hydrogen ions.

Hydrocortisone (Cortef, Solu-Cortef, A-Hydrocort)

Hydrocortisone is the drug of choice for glucocorticoid replacement because of its mineralocorticoid activity and glucocorticoid effects. A double or triple dose is required for febrile illnesses. Doses as high as 10 times the maintenance level may be needed in the context of severe stress (eg, from trauma, critical illness, or surgery).


Fludrocortisone is used as partial replacement therapy for primary and secondary adrenocortical insufficiency.


Somatostatin Analogues

Class Summary

Somatostatin analogues inhibit growth hormone (GH) secretion and adenoma growth in somatotroph adenomas. They are used in treatment of patients with acromegaly and hormone-secreting tumors.

Octreotide (Sandostatin)

Octreotide is a potent, long-acting analogue of somatostatin. Like natural somatostatin, it inhibits GH secretion, insulin secretion and glucagon secretion. After intravenous (IV) administration, basal serum GH, insulin, and glucagon levels are lowered. Octreotide also inhibits prolactin secretion via vasoactive intestinal peptide (VIP)-mediated and thyrotropin-releasing hormone (TRH)-mediated secretion of prolactin.


Antiparkinson Agents, Dopamine Agonists

Class Summary

Dopamine receptor agonists have been used as adjuncts to octreotide for inhibiting GH release from somatotroph adenomas. Some of them have dopaminergic properties that inhibit prolactin secretion.

Bromocriptine (Parlodel)

Bromocriptine is a semisynthetic ergot alkaloid derivative that is a strong dopamine D2-receptor agonist and a partial dopamine D1-receptor agonist. It has been successful in further reducing GH levels in acromegalic patients treated with octreotide, though it is not generally a first-line therapy. It is indicated for amenorrhea or galactorrhea secondary to hyperprolactinemia in the absence of primary tumor.


Cabergoline has been successful in further reducing GH levels in acromegalic patients treated with or without octreotide, though it is not generally a first-line therapy.



Class Summary

Bisphosphonates are stable analogues of pyrophosphate and potent inhibitors of bone resorption and bone turnover. They are used to prevent the bone resorption and pain of polyostotic fibrous dysplasia (PFD).

Pamidronate (Aredia)

Pamidronate has been successful in treating the pain of PFD; it may have some benefit in increasing bone mineral density as well.

Alendronate (Fosamax, Binosto)

Alendronate has been successful in treating the pain of PFD; it may have some benefit in increasing bone mineral density as well. It offers the additional benefit of oral administration.

Ibandronate (Boniva)

Ibandronate increases BMD and reduces the incidence of vertebral fractures. Ibandronate increases BMD at the spine by 5.7-6.5% and the hip by 2.4-2.8%. It reduces vertebral fractures by 50% with intermittent (nondaily) dosing over 3 years; it has no effects on reduction of nonvertebral fractures. Ibandronate is approved for the treatment and prevention of postmenopausal osteoporosis. It is available as a 150-mg oral tablet and intravenous solution.

Risedronate (Actonel, Atelvia)

Risedronate is a potent antiresorptive agent that does not affect bone mineralization. The inclusion of an amino group within the heterocyclic ring makes risedronate one of the most potent antiresorptive bisphosphonates. As with other bisphosphonates, risedronate inhibits osteoclast formation and activity. Risedronate increases BMD at the spine by 5.4% and the hip by 1.6%. It reduces vertebral fractures by 41% and nonvertebral fractures by 39% over 3 years. It is approved for the treatment and prevention of postmenopausal osteoporosis, male osteoporosis, and glucocorticoid-induced osteoporosis.

Zoledronic acid (Reclast)

Zoledronic acid inhibits bone resorption by altering osteoclast activity and by inhibiting normal endogenous, as well as tumor-induced, mediators of bone degradation. Like other bisphosphonates, zoledronic acid binds to hydroxyapatite crystals in mineralized bone matrix. The binding to calcium phosphates slows the dissolution of hydroxyapatite crystals and inhibits the formation and aggregation of these crystals. It increases BMD at the spine by 4.3-5.1% and at the hip by 3.1-3.5%, as compared with placebo. It reduces the incidence of spine fractures by 70%, hip fractures by 41%, and nonvertebral fractures by 25% over 3 years.

Zoledronic acid is approved for the treatment and prevention of postmenopausal osteoporosis, glucocorticoid-induced osteoporosis, osteoporosis in men, and Paget disease of bone. It is contraindicated in patients with severe renal failure.


Estrogen Receptor Antagonists

Class Summary

Estrogen receptor antagonist therapy represents a newer approach to the treatment of persistent estradiol elevation in girls.

Raloxifene (Evista)

The biological actions of raloxifene are largely mediated through binding to estrogen receptors, which results in activation of estrogenic pathways in some tissues (agonism) and blockade of estrogenic pathways in others (antagonism). Raloxifene increases BMD at the spine and the hip. It reduces the incidence of spine fractures by 30-55% over 3 years. Raloxifene is approved for the prevention and treatment of postmenopausal osteoporosis in women. It is available as 60-mg tablets that are given orally daily. Adverse reactions commonly seen include hot flashes, leg cramps, peripheral edema, flu syndrome, arthralgia, and sweating.

Tamoxifen (Soltamox)

Tamoxifen competitively binds to estrogen receptors, producing a nuclear complex that decreases DNA synthesis and inhibits estrogen effects. It blocks the end-organ effects of abnormal estrogen exposure in prepubertal girls.


Antithyroid Agents

Class Summary

Antithyroid agents block production of thyroid hormone in functional thyroid nodules and are used in palliative treatment of hyperthyroidism.

Propylthiouracil (PTU)

Propylthiouracil is a derivative of thiourea that inhibits organification of iodine by the thyroid gland. It blocks oxidation of iodine in the thyroid gland, thereby inhibiting thyroid hormone synthesis; it also inhibits conversion of thyroxine to triiodothyronine (and thus possesses an advantage over other agents).

Methimazole (Tapazole)

Methimazole inhibits thyroid hormone by blocking oxidation of iodine in the thyroid gland. It is used to decrease the production of thyroid hormone in functional thyroid nodules associated with MAS. Hyperthyroidism in MAS, unlike autoimmune-mediated hyperthyroidism, is likely to require long-term treatment.


Vitamins, Fat-Soluble

Class Summary

Metabolic agents are indicated to correct deficiencies leading to hypoparathyroidism, as well as to treat hypercalcemia and prevent bone loss.

Ergocalciferol (Calciferol, Drisdol)

Ergocalciferol stimulates absorption of calcium and phosphate from the small intestine and promotes release of calcium from bone into blood.