Pituitary hyperplasia secondary to acquired hypothyroidism: case report
© Franceschi et al; licensee BioMed Central Ltd. 2011
Received: 24 January 2011
Accepted: 7 April 2011
Published: 7 April 2011
Objective and Importance
despite recent progress in imaging, it is still difficult to distinguish between pituitary adenoma and hyperplasia, even using Magnetic Resonance Imaging (MRI) with gadolinium injection. We describe an example of reactive pituitary hyperplasia from primary hypothyroidism that mimicked a pituitary macroadenoma in a child.
a 10 year old boy presented with headache and statural growth arrest. MRI revealed an intrasellar and suprasellar pituitary mass. Endocrine evaluation revealed primary hypothyroidism.
the patient was started on levothyroxine with resolution of the mass effect.
primary hypothyroidism should be considered in the differential diagnosis of solid mass lesions of the pituitary gland. Examination of thyroid function in patients with sellar and suprasellar masses revealed by MRI may avoid unnecessary operations which can cause irreversible complications.
There are many causes of sellar and suprasellar mass, and pituitary enlargment secondary to primary hypothyroidism has been previously described [1–5]. It results from the loss of thyroxine feedback inhibition and the subsequent overproduction of thyrotropin-releasing hormone (TRH) . Despite recent progress in imaging techniques, it is not possible to distinguish between TSH-producing macroadenoma and hyperplasia of pituitary thyrotroph cells on CT and MR scans. In such cases, repeat MRI after therapy with thyroxine may provide a definitive diagnosis and eliminate unnecessary surgery: unlike adenoma, pituitary hyperplasia resolves after thyroid hormone replacement therapy .
History and Physical Examination
A 10 year old boy, born at term in Morocco from non-consanguineous parents after an uncomplicated pregnancy, presented at his local hospital with occipital headache over the last three months and height growth arrest: during the previous 2 years he had grown 1 cm, declining from the 75-90th percentile to the 25th, while his weight had passed from the 50th to the 75th percentile in the last year. He did not complain of vomiting, tiredness or any other symptoms.
His past and familial history was unremarkable and his cognitive development normal. On physical examination, he presented with height 136 cm (25th percentile), weight 42 kg (75th percentile), prepubertal status, blood pressure 120/67 mmHg, pulse rate 72 bpm, and non-palpable thyroid gland. Because of persistent headache he was referred to the neurologist at his local hospital and the examination was normal, as were the fundus oculi and visual fields.
Radiographic and laboratory data
After endocrine consultation, blood tests were done: full blood count, erythrocyte sedimentation rate, renal and liver function and anti-coeliac screening were
Hormonal pattern at diagnosis and during follow up
3 months later
6 months later
Free T4, pmol/L
Free T3, pmol/L
Due to the loss of thyroxine feedback inhibition and the subsequent overproduction of thyrotropin-releasing hormone (TRH), long-standing hypothyroidism results in hyperplasia of the thyrotroph cells and subsequent enlargement of the pituitary gland . The incidence of pituitary hyperplasia in patients with hypothyroidism varies from 25% to 81% , high incidence (70%) is reported in patients with TSH levels ≥50 μIU/m 8 l . Because TRH also has a weak stimulatory effect on lactotroph cells, mild to moderate hyperprolactinemia may also occur in about three-quarters of patients . Nevertheless in our patient the slight increase in prolactin was probably due to the compression of the infundibulum by the mass, rather than to lactotroph hyperplasia.
Children with pituitary hyperplasia and primary hypothyroidism rarely present with neurological symptoms secondary to sellar expansion (3%). Their complaints at presentation are associated with hypothyroidism and abnormal puberty . Most children present with symptoms of growth arrest due to primary hypothyroidism, and growth hormone (GH) production may be decreased because thyroxine is one of the factors stimulating GH synthesis . Long-standing primary hypothyroidism may also lead to irreversible pituitary injury, which can lead to a deficiency in one or more pituitary hormones . Therefore in our patient persistent headache has to be attributed to hypothyroidism, even if the exact mechanism is not clear. Moreover reduced IGF-1 was probably secondary to transitory reduced GH synthesis.
Despite recent progress in imaging, it is still difficult to distinguish between a pituitary adenoma and hyperplasia, even using MRI with gadolinium injection. On imaging studies, secondary pituitary hyperplasia is often characterized by a homogeneously enhancing lesion that may progress rapidly following the onset of a hypothyroid state . Interpretation of a pituitary mass without an endocrine investigation can lead to unnecessary surgery which can cause irreversible complications [9–11]. Differential diagnosis with TSH secreting adenoma can be made by means of inappropriatey normal/high range values of T3 and T4. Nevertheless the sequence and time course of hypothyroidism and pituitary hyperplasia have not been clarified . Concomitant diagnosis of hypothyroidism and pituitary hyperplasia are described in the literature , but two additional scenarios have been reported: a) normal thryoid function may be found in patients with a pituitary mass revealed by MR imaging. Re-examination a few weeks later is recommended because initial normal thyroid function may mask the diagnosis of hypothyroidism-related pituitary hyperplasia in these patients ; b) in other patients rapid progression of hyperplasia may develop after hypothyroidism .
Thyroid hormone replacement therapy led to a decrease in the size of the gland in 85% of patients with pituitary enlargement who underwent follow-up MR examinations . Surgery should be reserved for decompression of the optic chiasm or to obtain a pathological diagnosis in the case of a pituitary mass which does not respond to, or worsens under, thyroid hormone replacement . In our patient, baseline thyroid function tests were consistent with primary hypothyroidism secondary to chronic autoimmune thyroiditis and repeat pituitary MRI after 5 months of levothyroxine therapy revealed complete regression of the pituitary mass. Based on the combined clinical findings, hormonal studies, and repeat MRI findings, the diagnosis of pituitary hyperplasia secondary to primary autoimmune hypothyroidism was made.
Primary hypothyroidism should be considered in the differential diagnosis of solid mass lesions of the pituitary gland, particularly in children with short stature. Examination of thyroid function in patients with sellar and suprasellar masses revealed by MR imaging may avoid unnecessary operations.
Written informed consent was obtained from the patient's relatives for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
- Joshi AS, Woolf PD: Pituitary hyperplasia secondary to primary hypothyroidism: a case report and review of the literature. Pituitary. 2005, 8: 99-103. 10.1007/s11102-005-3281-8.View ArticlePubMedGoogle Scholar
- Eom KS, See-Sung C, Kim JD, Kim JM, Kim TY: Primary hypothyroidism mimicking a pituitary macroadenoma: regression after thyroid hormone replacement therapy. Pediatr Radiol. 2009, 39 (2): 164-167. 10.1007/s00247-008-1012-9.View ArticlePubMedGoogle Scholar
- Simşek E, Simşek T, Savaş-Erdeve S, Erdoğmuş B, Döşoğlu M: Pituitary hyperplasia mimicking pituitary macroadenoma in two adolescent patients with long-standing primary hypothyroidism: case reports and review of literature. Turk J Pediatr. 2009, 51 (6): 624-630.PubMedGoogle Scholar
- Xu AJ, Li T: Pituitary hyperplasia secondary to primary hypothyroidism in children: report of 8 cases. Zhongguo Dang Dai Er Ke Za Zhi. 2010, 12 (1): 17-20.PubMedGoogle Scholar
- Lee CY, Hsu HH, Lai HY, Lee ST: Rapid progression of hypothyroidism-related pituitary hyperplasia. J Neurosurg Pediatr. 2008, 2 (3): 212-214. 10.3171/PED/2008/2/9/212.View ArticlePubMedGoogle Scholar
- Koller KJ, Wolff RS, Warden MK, Zoeller RT: Thyroid hormones regulate levels of thyrotropin-releasing-hormone mRNA in the paraventricular nucleus. Proc Natl Acad Sci USA. 1987, 84 (20): 7329-7333. 10.1073/pnas.84.20.7329.PubMed CentralView ArticlePubMedGoogle Scholar
- Beck-Peccoz P, Brucker-Davis F, Persani L, Smallridge RC, Weintraub BD: Thyrotropin-secreting pituitary tumors. Endocr Rev. 1996, 17 (6): 610-638.PubMedGoogle Scholar
- Khawaja NM, Taher BM, Barham ME, Naser AA, Hadidy AM, Ahmad AT, Hamamy HA, Yaghi NA, Ajlouni KM: Pituitary enlargement in patients with primary hypothyroidism. Endocr Pract. 2006, 12 (1): 29-34.View ArticlePubMedGoogle Scholar
- Shimono T, Hatabu H, Kasagi K, Miki Y, Nishizawa S, Misaki T, Hiraga A, Konishi J: Rapid progression of pituitary hyperplasia in humans with primary hypothyroidism: demonstration with MR imaging. Radiology. 1999, 213 (2): 383-388.View ArticlePubMedGoogle Scholar
- Chan AW, MacFarlane IA, Foy PM, Miles JB: Pituitary enlargement and hyperprolactinaemia due to primary hypothyroidism: errors and delays in diagnosis. Br J Neurosurg. 1990, 4 (2): 107-112. 10.3109/02688699008992708.View ArticlePubMedGoogle Scholar
- Riedl S, Frisch H: Pituitary hyperplasia in a girl with gonadal dysgenesis and primary hypothyroidism. Horm Res. 1997, 47 (3): 126-130. 10.1159/000185447.View ArticlePubMedGoogle Scholar
- Samaan NA, Osborne BM, Mackay B, Leavens ME, Duello TM, Halmi NS: Endocrine and morphologic studies of pituitary adenomas secondary to primary hypothyroidism. J Clin Endocrinol Metab. 1977, 45 (5): 903-911. 10.1210/jcem-45-5-903.View ArticlePubMedGoogle Scholar
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