Microfollicular Thyroid Adenoma and Congenital Goitrous Hypothyroidism

1294 Archives ofDisease in Childhood 1992; 67: 1294-1295

Microfollicular thyroid adenoma and congenital Arch Dis Child: first published as 10.1136/adc.67.10.1294 on 1 October 1992. Downloaded from goitrous hypothyroidism

A J Alabbasy, L Delbridge, R Eckstein, C Cowell, M Silink

Abstract diagnosis of congenital goitrous hypothy- Three patients with congenital goitrous roidism secondary to peroxidase deficiency hypothyroidism are reported. They were was made on the basis of avid uptake on thy- treated with adequate thyroxine replace- roid scan and a positive perchlorate discharge ment and developed well defined micro- test. The initial thyroid function tests were tri- follicular thyroid adenomas despite being iodothyronine resin uptake 0-65 nmoil (nor- euthyroid clinically and biochemically mal 0-801-20), thyroxine 18 nmolA (normal throughout their clinical course. Patients 100-215), FTI 12 (normal 75-200) and TSH with congenital goitrous hypothyroidism 620 mU/l (normal 1-15). appear to be at increased risk of develop- Her thyroxine replacement was monitored ing thyroid adenoma in childhood despite at intervals of three months, and through- the use of replacement thyroxine treat- out the next four years the TSH remained ment in physiological doses. <7 mU/l except for two occasions (at the age of 2 and 4 years) when it was transiently (Arch Dis Child 1992;67:1294-5) increased, reaching concentrations of 17-5 Congenital goitrous hypothyroidism due to a and 115 mU/l respectively. The FTI primary biochemical defect of thyroid biosyn- remained in the range 126-192 at all times thesis accounts for approximately 10-15% of (normal 50-180). all congenital hypothyroidism detected at At the age of 4-25 years a thyroid nodule screening in Western countries.' The goitre is was detected clinically. A thyroid scan presumed to be due to thyrotrophin stimu- revealed a hyperfunctioning thyroid nodule lating hormone (TSH) overstimulation in in the left lobe. At operation a 2 cm diameter response to low thyroid hormone concentra- microfollicular adenoma of fetal type was tions causing hyperplasia of the dysfunctional removed. A similar 0-2 cm adenoma was thyroid tissue.2 This process may lead to the present in the adjacent thyroid tissue. The development of adenomatous growth and follicular epithelial cells showed variable rarely malignant transformation.2 We report hyperplasia and nuclear enlargement (figure). three patients with this condition who devel- http://adc.bmj.com/ oped well defined, encapsulated microfollicular adenomas despite adequate thyroxine replace- ment. Case reports CASE 1

A boy was referred at the age of 3*3 years with on October 1, 2021 by guest. Protected copyright. a goitre present since birth. Clinically he was euthyroid. Investigations revealed free thyrox- ine index (Ff1) 95 (nornal 65-150), TSH 32 mUll (normal <7), and a diffusely enlarged goitre with avid uptake on a technetium thy- The Ray Wlliams roid scan. The perchlorate discharge test did Institute ofPaediatric not a Endocrinology, suggest peroxidase deficiency. Royal Aledra When thyroxine treatment was given the Hospital for Children, gland regressed to a nornal size. Thyroxine PO Box 34, Camperdon requirements were monitored by thyroid func- NSW 2050, tion studies and TSH measurements at inter- Australia vals of three to six months. He remained A J Alabbasy euthyroid clinically and biochemically and at C Cowell M Silink the age of 11 -7 years presented with a thyroid nodule. Ultrasonography revealed mildly Endocrine Unit, enlarged thyroid lobes, and a well defined Royal North Shore Hospital, St Leonards, solid mass in the left lobe. At operation a NSW, Austraia 1-8 cm diameter microfollicular adenoma of L Dedbridge fetal type was removed. R Eckstein Correspondence to: CASE 2 Professor Sulink. This girl was detected on the neonatal screen- Adnoma and adjacent hyperplastic thyroid tissue of Accepted 11 May 1992 ing programme at the age of 2 weeks and a case 2 (haematoxylin and eosin xl30). Microfoliauar throid aderma and congenital goitru hypohroidism 1295

CASE 3 over time and typically are very cellular, show- This boy had congenital goitrous hypo- ing embryonal or fetal architecture.2 As a thyroidism diagnosed at 9 months of age result the histological distinction between Arch Dis Child: first published as 10.1136/adc.67.10.1294 on 1 October 1992. Downloaded from when he presented with the classical clinical adenoma and nodule may not be clear cut. features of hypothyroidism. This was con- Hyperplasia and cellular pleomorphism may finned by the thyroxine measurement of 30 be so marked as to mimic malignant transfor- nmol/ (normal 75-160) and TSH >400 mU/l mation, but genuine malignancy appears to be (nornal <7). The thyroid scan showed an a rare event, only six cases being accepted in enlarged thyroid gland with moderately the literature review of Cooper et al.2 enhanced but uniform uptake. In contrast to our patients, most cases pre- Replacement thyroxine treatment was star- viously described were long term hypothyroid ted with a good clinical and biochemical or on sporadic thyroxine replacement with response. His thyroxine and TSH remained excessive stimulation of TSH. Our patients within normal ranges throughout the next 11 unexpectedly developed true adenomas de- years. spite strict clinical and biochemical follow At the age of 12-5 years he presented with a up, suggesting sensitivity of the patients' thy- nine month history of a nodular goitre. On roid follicles to the effects of normal TSH palpation the left lobe was 5x4 cm and the concentrations. This is supported by the his- right 35x4 cm. Thyroid ultrasound identified tological observation of diffuse hyperplasia multiple solid nodules involving both lobes of in cases 2 and 3 as well as the presence of the thyroid gland. The largest mass measured multiple small adenomas in case 3. Recent 3x3x3'5 cm in the left lobe and corresponded evidence suggests that there are many other to a large well demarcated solid nodule. thyroid growth promoting agents including Total thyroidectomy was performed. The vasoactive inhibitory peptide4 and epidermal cut surface showed several well demarcated growth factor.5 colloid nodules with a 2-5 cm diameter fleshy We conclude that although patients with nodule in the left lower lobe. The large nod- congenital goitrous hypothyroidism are par- ule in the left lobe was well circumscribed fol- tially protected from the development of licular adenoma showing microfollicular and nodular goitre by adequate thyroxine replace- embryonal growth pattern. Elsewhere in the ment treatment, they remain at risk of de- thyroid tissue there were numerous nodules veloping follicular adenomas as a result of showing quite variable cellularity. persistent low concentration TSH stimu- lation. Thyroxine replacement treatment will reduce but not eliminate the development of Discussion adenomas. These patients had hypothyroidism secondary to dyshormonogenesis. The positive per- 1 Fisher DA, Dussault JH, Folley TP, et aL Screning for congenital hypothyroidism: results of screening one chlorate discharge test in case 2 suggests an million North American infsnts. Pediar 1979;94:700-5. organification defect,3 while the normal per- 2 Cooper DS, Axehrod L, DeGroot J, Vickery AL, MaoofF. Congenital goitre and the development of metastatic http://adc.bmj.com/ chlorate discharge test in case 1 would suggest follicular carcinoma with evidence for a leak of non- a diagnosis of one of the other metabolic hormonal iodide: clinical, pathological, inetic and bio- chemical studies and a review of the literature. I Chs abnormalities such as deiodinase, coupling, or EndocrinoMetab 1981;52:294-306. thyroglobulin defects.3 All remained euthyroid 3 Stanbury JB, Dumont JE. Familial goitre and related dis- orders. In: Stanbury JB, Wyngaarden J, Fredrickson DS clinically and biochemically but despite the Goldstein JL, Brown Ms, eds. The meaboic basis of seemingly adequate thyroxine replacement inheddisea New York: McGraw-Hill, 1983:231-69. 4 Siperstein AE, Miller Clark OH. Stimulatory effect of they developed microfollicular adenomas. vasoactive intestinal R,poeptide on human normal and

neoplastic thyroid tissue. Ssi 1988;104:985-91. on October 1, 2021 by guest. Protected copyright. Histologically, congenital goitrous hypo- 5 Westermark K, Westermark B,Xaalson FA, Ericson LE. thyroidism is characterised initially by diffuse Location of epidermal growth factor receptors onproine thyroid follicle cells and receptor regulation cythy_ hyperplasia. Nodules and adenomas develop rotropin. Endociology1985;118146.