title: Hyperthyroidism unmasked several years after the medical and radiosurgical treatment of an invasive macroprolactinoma inducing hypopituitarism: a case report.
abstract: BACKGROUND
  Measuring thyroid stimulating hormone levels alone may be insufficient to appropriately evaluate thyroid function. Reduced thyroid stimulating hormone levels associated to normal/reduced FT4 levels should prompt investigation of pituitary function, on suspicion of hypopituitarism. Pituitary macroadenomas are the most common cause of hypopituitarism; among these, macroprolactinomas are usually treated with dopamine-agonist therapy. Hypopituitarism does not preclude the development of primary hyperthyroidism. This report describes the case of a patient with a final diagnosis of macroprolactinoma inducing hypopituitarism, who subsequently developed hyperthyroidism due to a toxic thyroid nodule.
  
  
  METHODS
  A 62-year-old man underwent biochemistry and thyroid function assessment for asthenia. Reduced thyroid stimulating hormone levels were associated to slightly decreased FT4 levels and low-normal FT3 levels; thyroid ultrasonography showed a multinodular goiter. Thyroid scan with (99m)Tc-pertechnetate revealed an autonomous left nodule with suppression of the surrounding parenchyma. Pituitary investigation showed partial hypopituitarism associated to increased prolactin levels: 182-200 ng/ml. Magnetic resonance imaging revealed a large (2.2 cm) invasive macroadenoma. To avoid a possible high-dose hook effect, the patient's serum was diluted; the resulting PRL levels of around 1800 ng/ml prompted the final diagnosis of macroprolactinoma. Reduced libido and erectile dysfunction were ascertained. In addition to replacement therapy with L-thyroxine and testosterone, cabergoline was started and was progressively increased to high doses (4 g/week); this yielded a significant but incomplete reduction of PRL levels (63-99 ng/ml). Sexual function improved. The macroadenoma shrank over the first two years of therapy, but subsequently enlarged slightly. Following stereotactic radiosurgery, the tumor stabilized and prolactin almost normalized (22 ng/ml) on therapy. Over the years, thyroid nodule volume was unmodified, but hyperthyroidism on L-thyroxine therapy was found, and increased FT3 levels with suppressed thyroid stimulating hormone levels were confirmed off-therapy. Thyroid scan confirmed the left autonomous nodule, which was successfully treated with methimazole.
  
  
  CONCLUSIONS
  Reduced thyroid stimulating hormone levels associated to normal/reduced free-thyroid hormone levels may be the first clue to unsuspected hypopituitarism. Moderately increased prolactin levels in the presence of a large macroadenoma warrant serum dilution in order to avoid a possible hook effect. Stereotactic radiosurgery is a useful non-invasive tool in the management of pituitary tumors. A pre-toxic thyroid nodule with low secretory activity may initially be masked by the coexistence of secondary hypothyroidism, but may lead to overt hyperthyroidism over time.
authors.affiliation: Department of Endocrinology, Galliera Hospital, Mura Delle Cappuccine 14, 16128 Genova, Italy. luca.foppiani@galliera.it
authors.forename: Luca
authors.initials: L
authors.lastname: Foppiani
authors.forename: Antonio
authors.initials: A
authors.lastname: Ruelle
authors.forename: Paolo
authors.initials: P
authors.lastname: Cavazzani
authors.forename: Patrizia
authors.initials: P
authors.lastname: Del Monte