A 21 year old woman presenting with galactorrhoea, hyperprolactinaemia, and a pituitary mass on magnetic resonance imaging (MRI) is described who was referred to us before planned pituitary surgery. Although a thorough history did not suggest hypothyroidism, laboratory studies revealed profound primary hypothyroidism. At that time, pituitary MRI showed homogeneous enlargement of the pituitary gland consistent with pituitary hyperplasia due to primary hypothyroidism. With thyroid hormone replacement therapy the galactorrhoea resolved, concentrations of prolactin and thyroid hormones returned to normal, and the pituitary shrunk to normal size within two months. This case illustrates that primary hypothyroidism can present only with galactorrhoea and pituitary mass, and should therefore be considered in the differential diagnosis of hyperprolactinaemia and pituitary enlargement.
- primary hypothyroidism
- pituitary mass
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Galactorrhoea is a common symptom of hyperprolactinaemia in premenopausal women. The most frequent causes of pathological hyperprolactinaemia are pituitary tumours and drugs with dopamine antagonist properties, whereas less common aetiologies include hypothalamic disease, chronic renal failure, liver cirrhosis, breast disease, chest wall trauma, spinal cord lesion, and primary hypothyroidism.
However, in patients with primary hypothyroidism galactorrhoea is a rare feature compared with the typical symptoms such as fatigue, weight gain, cold intolerance, constipation, dry skin, and myopathy.
We describe a patient initially presenting with galactorrhoea and pituitary enlargement, but without any other characteristic symptoms suggesting primary hypothyroidism.
A 21 year old woman (born in 1977) had a two year history of increasing galactorrhoea. Six months earlier, she had started a hormonal contraception with a triphasic combination of oestrogens (ethinyloestradiol) and progestins (gestodene). In the past, her menstrual cycle had been normal and regular, since menarche at the age of 13 (in 1990). In October 1997 mild hyperprolactinaemia (prolactin 37.7 μg/l) was found and magnetic resonance imaging (MRI) revealed a 8 mm sized pituitary tumour.
In January 1998, she was admitted to our outpatient endocrinology division for preoperative evaluation of the pituitary tumour and galactorrhoea. She complained of galactorrhoea cyclically increasing before menstrual bleeding. She did not suffer any other symptoms nor take any medication except for the oral contraceptive. She went to a teacher training college and was fit. Physical examination revealed a healthy appearing woman of normal weight (59.5 kg) and height (169 cm) with a regular heart rate of 64 beats/min, a blood pressure of 132/88 mm Hg, normal voice, skin, hair, nails, and thyroid gland. Bilateral expressible galactorrhoea was present. The ankle jerks showed a markedly delayed relaxation phase. Haematological tests revealed a low haemoglobin of 113 g/l (normal range 123–158 g/l) and packed cell volume of 0.353 (0.37–0.47). Blood chemistry showed raised concentrations of total cholesterol of 9.3 mmol/l and total creatine kinase activity of 917 U/l (<150 U/l). The endocrinological tests confirmed hyperprolactinaemia (prolactin 118 μg/l, normal range 2–20) and disclosed primary hypothyroidism with low free thyroxine (5.1 pmol/l, normal range 8.5–19.0), low free triiodothyronine (1.5 pmol/l, normal range 3.5–6.2), and markedly increased thyroid stimulating hormone (TSH) (506.75 mU/l, normal range 0.1–4.0). Thyroglobulin and thyroid peroxidase antibodies were raised, suggesting autoimmune thyroid disease.
Pituitary MRI performed at that time showed homogeneous enlargement of the pituitary gland (12 × 10 mm in diameter) with a convex suprasellar expansion and without any signs of a focal lesion, consistent with pituitary hyperplasia due to primary hypothyroidism (fig 1A).
The patient was advised to stop taking the oral contraceptive, and thyroxine replacement was initiated with 50 μg levothyroxine daily for two weeks and then increased to 100 μg daily. One month later the galactorrhoea resolved, and spontaneous regular menstrual bleeding returned after six weeks. In April 1998, upon two months of thyroxine substitution, free thyroxine (16.4 pmol/l), free triiodothyronine (4.4 pmol/l) and prolactin (12.7 μg/l) concentrations were normal, and TSH was only slightly raised (7.66 mU/l). On repeat MRI of the sellar region, the volume of the pituitary had shrunk to normal size (8.5 × 9 mm in diameter; fig 1B).
The presentation of our patient with galactorrhoea, hyperprolactinaemia, and a pituitary mass suggested, at first glance, the diagnosis of prolactinoma rather than primary hypothyroidism. Hypothyroidism can cause a broad range of signs and symptoms. Manifestation with galactorrhoea is rare, but well known.1-3 Prolactin concentrations greater than 25 μg/l were found in about 10% of patients with hypothyroidism.4Hyperprolactinaemia results from increased thyrotrophin releasing hormone (TRH) production and increased sensitivity of lactotrophs to TRH.5
Exogenous oestrogen supply by oral contraceptives may favour hyperprolactinaemia as well as galactorrhoea by actions at both the pituitary and the breast level.5 6 In addition, hypothyroidism slows the metabolism of oestrogen and thereby may further increase the effect of ethinyloestradiol. Profound hypothyroidism often causes hypogonadism with amenorrhoea. In states of oestrogen deficiency, hyperprolactinaemia rarely causes galactorrhoea. Galactorrhoea typically occurs in hypothyroid patients with hyperprolactinaemia and normal or high concentrations of oestrogens, especially during hormonal contraception and after pregnancy.7
It is known that patients with longstanding primary hypothyroidism may have pituitary enlargement visible on MRI or computed tomography.8 This enlargement is related to chronically decreased circulating thyroid hormones and subsequent hypersecretion of TSH and thyrotroph cell hyperplasia. The pituitary hyperplasia could be mistaken for a pituitary tumour, especially prolactinoma, and patients could undergo unnecessary operation with considerable complications.3 9
Thyroxine replacement for primary hypothyroidism resolves galactorrhoea and amenorrhoea, causes the prolactin concentrations to return to normal, and results in rapid regression of pituitary size (fig1B).5 8 10 Thus, it is important to check thyroid function in all patients with hyperprolactinaemia as well as in patients with pituitary enlargement before the diagnosis of prolactinoma is made. Other secondary causes of hyperprolactinaemia should also be excluded.
Profound biochemical hypothyroidism may exist in apparently healthy individuals with minimal clinical evidence of hypothyroidism.
Not every patient with galactorrhoea, hyperprolactinaemia, and a pituitary mass has a prolactinoma.
Hypothyroidism should always be considered in the differential diagnosis of hyperprolactinaemia and in the differential diagnosis of pituitary enlargement.