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Indications for Therapy and for Neurosurgery in Patients with Prolactinomas

In contrast to macroadenomas, for which therapy is routinely indicated, microadenomas do not always require treatment. For patients with microadenomas who do not have these indications, symptoms and prolactin levels can be monitored, and MRI can be used to follow the size of the tumor.
Indications for Therapy in Patients with Prolactinomas
  • Macroadenoma
  • Enlarging microadenoma
  • Infertility
  • Bothersome galactorrhea
  • Gynecomastia
  • Testosterone deficiency
  • Oligomenorrhea or amenorrhea
  • Acne and hirsutism

Given the efficacy of medical therapy, only a small minority of patients with prolactinomas require transsphenoidal surgery or radiation therapy. Surgical cure rates, which are highly dependent on surgical skill and tumor anatomy, approach 80 to 90% for microadenomas but are less than 50% for macroadenomas.
Indications for Neurosurgery in Patients with Prolactinomas
  • Increasing tumor size despite optimal medical therapy
  • Pituitary apoplexy
  • Inability to tolerate dopamine agonist therapy
  • Dopamine agonist–resistant macroadenoma
  • Dopamine agonist–resistant microadenoma in a woman seeking fertility, if ovulation induction is not appropriate
  • Persistent chiasmal compression despite optimal medical therapy
  • Medically unresponsive cystic prolactinoma
  • In women seeking fertility, macroadenoma in close proximity to optic chiasm despite optimal medical therapy (prepregnancy debulking recommended)
  • Cerebrospinal fluid leak during administration of dopamine agonist
  • Macroadenoma in a patient with a psychiatric condition for which dopamine agonists are contraindicated

  1. Klibanski A. Clinical practice. Prolactinomas. N Engl J Med. 2010 Apr 1;362(13):1219-26. [Medline]
  2. Molitch ME. Medical management of prolactin-secreting pituitary adenomas. Pituitary. 2002;5(2):55-65.[Medline]

Guidelines for the Treatment of Asymptomatic Primary Hyperparathyroidism

The finding of hypercalcemia on routine biochemical testing or in the evaluation of postmenopausal women with osteoporosis is typically the initial clue to the diagnosis of primary hyperparathyroidism. The total serum calcium level, which combines both the free and albumin-bound components of circulating calcium, should be adjusted for the level of albumin. Measurement of ionized calcium may be useful in selected cases, such as in patients with hyperalbuminemia, thrombocytosis, Waldenström's macroglobulinemia, and myeloma; these patients may have elevated levels of total serum calcium, but normal levels of ionized serum calcium (artifactual hypercalcemia).

Measurement of serum PTH is the next step in the evaluation of hypercalcemia. An elevated level of PTH (or a level that is in an unexpected “normal” range) simultaneous with an elevated calcium level generally indicates a diagnosis of primary hyperparathyroidism. However, these laboratory findings may also occur with lithium or thiazide use, tertiary hyperparathyroidism associated with end-stage renal failure, and familial hypocalciuric hypercalcemia, and a medical and family history should be obtained to assess these possibilities. The finding of a normal level of albumin-adjusted or ionized serum calcium and an elevated level of PTH in patients with no other causes of secondary hyperparathyroidism is consistent with normocalcemic primary hyperparathyroidism. A low or undetectable PTH level rules out primary hyperparathyroidism and raises the possibility of cancer-associated hypercalcemia, often mediated by PTH-related protein, which does not cross-react with the PTH assay. If the PTH level is elevated in a person with a known malignant condition, the most likely diagnosis is concomitant primary hyperparathyroidism; ectopic production of PTH from a tumor is extremely rare.

Guidelines for the Treatment of Asymptomatic Primary Hyperparathyroidism
Variable Criteria for Surgery* Surveillance without Surgery 
Serum calcium level  
>1.0 mg/dl (0.25 mmol/liter) above upper limit of normal range 
Creatinine clearance (calculated)† Reduced to <60 ml/min Not recommended 
Bone mineral density 
 T score less than -2.5 at any site,‡ previous fragility fracture, or both 
Every 1–2 yr (three sites) 
Age <50 yr Not applicable 

* Surgery should also be recommended for patients in whom surveillance is not feasible.
† The estimated glomerular filtration rate (milliliters per minute per 1.73 m2 of body-surface area) should be calculated from the serum creatinine concentration, demographic characteristics (age, sex, and race or ethnic group), and other serum measurements (e.g., blood urea nitrogen and albumin concentrations) according to the following equation: 170×(serum creatinine in mg per deciliter) -0.999 ×(blood urea nitrogen in mg per deciliter) -0.170 ×(serum albumin in g per deciliter) 0.318 ×(age in years) -0.176 ×(0.762 if patient is female)×(1.180 if patient is black).
‡ Sites were the lumbar spine, total hip, femoral neck, and distal third of the radius. According to the International Society for Clinical Densitometry, z scores instead of T scores should be used in evaluating bone mineral density in premenopausal women and men younger than 50 years of age.


  1. Marcocci C, Cetani F. Clinical practice. Primary hyperparathyroidism. N Engl J Med. 2011 Dec 22;365(25):2389-97. [Medline] 
  2. Eastell R, Arnold A, Brandi ML, Brown EM, D'Amour P, Hanley DA, Rao DS, Rubin MR, Goltzman D, Silverberg SJ, Marx SJ, Peacock M, Mosekilde L, Bouillon R, Lewiecki EM. Diagnosis of asymptomatic primary hyperparathyroidism: proceedings of the third international workshop. J Clin Endocrinol Metab. 2009 Feb;94(2):340-50. [Medline]

Management Guidelines for Patients with Thyroid Nodules

As defined by the American Thyroid Association’s task force on the management of thyroid nodules and differentiated thyroid cancer, a thyroid nodule is a discrete lesion within the thyroid gland that is radiologically distinct from the surrounding thyroid parenchyma.
All patients with known or suspected thyroid nodules should undergo testing for thyrotropin levels, also known as ‘‘thyroid-stimulating hormone’’ (TSH). The risk of malignancy in a thyroid nodule has been shown to be significantly greater in patients with elevated TSH. Patients with a nodule and concomitant hypothyroidism have an adjusted odds ratio of malignancy in excess of 11.
The decision to refer for surgical evaluation depends to a great extent on the interpretation of the FNA. Reporting of FNA cytology varies between institutions and depends on the training and classification system used by the cytopathologist. Although the nomenclature may differ slightly, cytopathologists generally render their diagnoses within one of the following broad categories: nondiagnostic or inadequate, benign, cellular follicular lesion, follicular neoplasm, suspicious for malignancy, or malignant.

Management Guidelines for Patients with Thyroid Nodules

  1. Miller MC. The patient with a thyroid nodule. Med Clin North Am. 2010 Sep;94(5):1003-15. [Medline]
  2. American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer, Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, Mandel SJ, Mazzaferri EL, McIver B, Pacini F, Schlumberger M, Sherman SI, Steward DL, Tuttle RM. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2009 Nov;19(11):1167-214. [Medline]