Thyroid-stimulating hormone in thyroid dysgenesis

Thyroid-stimulating hormone in thyroid dysgenesis

7 14 Brie[ clinical and laboratory observations At this time, the signs and symptoms regressed, but a chest film revealed multiple large cystic area...

304KB Sizes 1 Downloads 94 Views

7 14

Brie[ clinical and laboratory observations

At this time, the signs and symptoms regressed, but a chest film revealed multiple large cystic areas in the left lower lobe (Fig. 2). The patient was asymptomatic at the time of the discharge 2 weeks post hydrocarbon ingestion. Physical examination 2 months later yielded normal results, except for decreased breath sounds over the left lung base. Chest films revealed extensive cystic involvement of the left lower lobe and a small portion of the right lower lobe (Fig. 3). The findings remained unchanged until 8 months postingestion when the chest

Thyroid-stimulating hormone in thyroid

dysgenesis Howard E. Kulin, M.D., Peter O. Kohler, M.D., Bert W. O'Malley, M.D., and William D. Odell, M.D., Ph.D. '* BETHESDA,


The Journal o[ Pediatrics November 1967

films revealed complete resolution of the pneumatoceles (Fig. 4). REFERENCES

I. Nelson, W. E.: Textbook of pediatrics, Philadelphia, 1964~ W. B. Saunders Company, p. 856. 2. Skarbek, A.: Pulmo~ary cysts following ingestion of household paraffin, Arch. Dis. Childhood 30: 457, 1955. 3. Baghdassarian, O. M., and Weiner, S.: Pneumatocele formation complicating hydrocarbon pneumonitis, Am. J. Roentgenol. 95: 104, 1964.

monly, the dysgenetic gland is not enlarged,' and T S H effects have not been demonstrated in these instances. By means of a recently developed radioimmunoassay, the thyroid-stimulating hormone 4 has been measured in 2 patients with sublingual thyroids without glandular hypertrophy and in 1 patient with athyreosis. The data indicate that T S H is present in large amounts in hypothyroidism secondary to both maldescent and absence of the thyroid gland. METHODS


N U 2r B E R


reports of patients with

dysgenetic thyroid tissue have appeared recently in the medical literature? -a The etiology of these defects, which include both the ectopic gland and athyreosis, remains speculative, and inadequate secretion of thyroidstimulating hormone (TSH) in utero is still considered as a possible mechanism? In patients in whom ectopic thyroid tissue has been hypertrophied, shrinkage during administration of exogenous thyroxin is evidence for increased secretion of endogenous TSH. z CornSection of Endocrinology, National Institute of Child Health and Human Development, and the Endocrinology Branch, National Cancer Institute, National Institutes of Health. *Present address, Endocrinology Division, Harbor General Hospital, Torranee~ Calif,, and Department of agadieine, University o/ Catilornla at Los Angeles,

Radioactive iodine (RAI) scans were performed on an Ohio Nuclear scanner with a 5 by 2 inch sodium iodide (thallium activated) crystal with the use of an 85 hole, 5 inch focusing collimator. Serum cortisol was determined by fluorimetric technique 5 and both growth hormone and T S H by radioimmunoassay. 4,~ The mouse uterine weight assay was utilized for measurement of total urinary gonadotropins. 7 T h e provocative test for both adrenocorticotropin hormone ( A C T H ) and growth hormone production was the intravenous injection of bacterial pyrogen, s CASE REPORTS AND RESULTS OF STUDIES

Case 1. Patient D. W. was delivered of a 25year-old diabetic, toxemic mother following a fullterm gestation. He weighed 7 pounds, 14 ounces, at birth and remained between the twenty-fifth and

Volume 71 Number 5

fiftieth percentiles for both height and weight through the first year of life. By age two years, however, his growth and development were clearly retarded. A protein-bound iodine (PBI) determination made at age 5w years was reported as 7.0 #g per cent, but no further evaluation for short stature and mental retardation was performed. Diagnosis of hypothyroidism was first made at age I0 years following admission to the Clinical Center, National Institutes of Health. At that time, his height was 103 cm. (less than the third percentile) and weight 22 kilograms (less than the third percentile). Mental retardation was marked (I.Q. = 47). Bone age was approximately 1 year, and the epiphyseal centers showed stippling which is characteristic of hypothyroidism. Tomograms of the sella turcica revealed a volume of 715 cubic millimeters, the normal for the patient's height being approximately 380 cubic millimeters.~ Pituitary function appeared normal, though highly elevated levels of thyroid stimulating hormone were present (see Table I). Growth hormone was not detected on 2 occasions in blood samples taken after a 12 hour fast and prior to the initiation of therapy with dessicated thyroid; it was detected after replacement therapy had begun. A 24 hour uptake of t zal was 5.9 per cent. A scan of the neck region with a 40 #c dose showed I T M to be concentrated in a small ( ( 1 era. in diameter) sublingual focus. He was initially treated with 60 mg. of dessicated thyroid per day. After one week, the TSH level remained elevated, but it was normal in samples examined 1 and 2 months later. Thyroid dosage was increased to 120 rag. daily after 5 months. Repeat I.Q. testing at age 11 years was essentially unchanged. By age 11~ he had grown 18 cm. since the time thyroid medication was begun, and bone age had increased to the 7 year level. Case 2. Patient V. T. was the product of a normal gestation and weighed 8 pounds, 11 ounces, at birth. Growth in the first 6 months of life was normal, but by age 3 years he was below the third percentile for height and between the third and tenth percentiles for weight. Roentgenograms obtained at that time showed a retarded bone age. He was started on thyroid replacement therapy which was taken only sporadically for the next 7 years. The patient was seen for the first time at the Clinical Center, National Institutes of Health at age 13N2. He had received no thyroid medi-

Brie[ clinical and laboratory observations

7 15

cation for 3 years. Upon physical examination height was 122 cm. (less than the third percentile) and weight, 25.7 kilograms (less than the third percentile). He had coarse hair, dry skin, and retarded dental development. Pertinent laboratory data are shown in Table I. Roentgenographic abnormalities included a moderately large sella turcica, mottled and irregular femoral epiphyses, and a bone age of 3 ~ years. I.Q. was 47. A thyroid scan using 20 #c of I T M showed no uptake over the neck but did reveal a focal area ( < 1.0 cm. in diameter) of increased actMty in the midposterior tongue. Plasma TSH was markedly elevated. Treatment was started with 12.5 #g of triiodothyronine per day; the dose was increased to 50 /~g over a period of one week. After 8 days of treatment, serum TSH had fallen to normal. Discharge medication was 200 /~g of L-thyroxin daily. Follow-up examination at age 14~ years indicated a gain in height of 12 cm. since onset of therapy and an advance in bone age to the 7 year level. Case 3. Patient T. G. was the product of an 8 ~ month, uncomplicated gestational period and weighed 4 pounds, 13 ounces, at birth. At age 3 months she weighed 6 pounds, 3y2 ounces, was constipated, ate poorly, and had a Iarge tongue. Her abdomen was protuberant, and an umbilical hernia was present. At age 6 months she was still below the third percentile for both height and weight. Laboratory studies done at that time revealed a PBI value of 1.8 ug per cent and an RAI uptake of 6 per cent in 24 hours. Treatment was begun with 45 mg. of dessicated thyroid daily, which was taken only sporadically. At 6 ~ years of age she was seen at the Clinical Center. Height was 100 era. (below the third percentile) and weight, 18 kilograms (third percentile). She had dry skin, an umbilical hernia, and dull facies. A 24 hour RAI uptake was 2 per cent, and a 42 /zc scanning dose of 1131 showed no functioning thyroid tissue in either the neck or sublingual area. Bone age was 3 ~ years. I.Q. tests indicated function at the level of a 2-year-old child. (See Table I for details of endocrine studies.) The level of thyroid-stimulating hormone was elevated far above normal. After therapy for 12 days with 50 #g of triiodothyronine daily, TSH levels became normal. The patient was discharged on 0.2 mg. of L-thyroxine daily and 2 months later displayed increased alertness and appetite. Skin texture was normal and height had increased 1.2 cm.

7 16

Brief clinical and laboratory observations

The Journal o[ Pediatrics November 1967

Table I. Summary of endocrine studies for each patient

Diagnosb Patient D. W. Lingual thyroid

TSH (#U./ml. is) Before R, t After R~

PBI (#g per cent)

RIU* (per cent in 24 hr.)

Cholesterol (rag. per cent)


< 4.5





< 4.5





~ 4.5




< 4.5

< 4.5


Patient V. T.

Lingual thyroid Patient T. G.

Total athyreosis Normal values



'~-Radioactlve iodine uptake. ~Normal range at the Clinical Center, National Institutes of Health.

COMMENTS Elevated levels of T S H characteristic of primary hypothyroidism were measured in all 3 patients. In addition, normal values for thyrotropin were determined after replacement therapy was initiated. Thus the ability of the pituitary gland of these subjects to respond to varying levels of thyroxin was clearly demonstrated. This information supports the contention that T S H function during embryonic stages was also normal, though such evidence is indirect. T S H activity has been detected in the fetal pituitary at 3 months gestation, 1~ a time coincident with the initial histological appearance of the thyrotroph. 1~ Thyroid descent, however, takes place considerably before this period, when the embryo is at the 2 to 3 mm. stage. As early as 10 weeks' gestational age, the fetal thyroid can produce all of the iodinated thyronines found in the adult? 2 TSH, then, would not seem to be necessary for thyroid migration, though animal work has revealed that the tropic hormone is necessary for complete development and function of the fetal thyroid gland? a Ectopic thyroid glands have been described more commonly in association with the symptoms that may arise from the hypertrophied

state or the finding of a mass at the base of the tonguC ~, la than as causes of cretinism. Only recently has thyroid dysgenesis been implicated as a significant cause of eretinism.1, 1~, 17 The reason for the appearance of goiter in some cases of maldescended thyroid remains unknown. The present study demonstrates that the absence of such hypertrophy is not caused by T S H deficiency. More likely, a critical amount of normal thyroid tissue must be present in order to enlarge under tropic stimulus. Alternatively, the adequacy of the blood supply to certain dysgenetic glands or tile presence of poorly differentiated cells may also be an explanation for the variation in gland size. SUMMARY Two patients with hypothyroidism and sublingual thyroids and one patient with athyreosis have been examined for T S H activity by radioimmunoassay. High levels of T S H were measured and could be suppressed by thyroid replacement, indicating normal responsiveness of the pituitary-thyroid axis. These data are further evidence against deficient T SH as a possible embryonic cause of thyroid dysgenesis.

Volume 71 Number 5

Baseline (a.m.) plasma eortisol (#g per cent) 16.0

Brie[ clinical and laboratory observations

Cortisol response to piromen (#g per cent)

Fasting growth hormone (m#g/ml.)

Growth hormone response to piromen (m#g/ml.)


Gonadotropins (mouse uterus units per 24 hr.)

Not tested

6.0 (after Rx)

Not tested

> 5 < 25 (one 48 hour specimen)





< I0 (two 24 hour specimens)





< 10 (two 24 hour specimens )

> 10.0 m#g/ml.

See reference 7


Increase over baseline levels by 5.0 m#g per cent

Appreciation is expressed to Dr. Griff T. Ross for his encouragement in this study and his critical review of this manuscript. REFERENCES

1. Little, G., Meador, C. K., Cunningham, R., and Pittman, J. A.: "Cryptothyroidism," the major cause of sporadic "athyreotic" cretinism, J. Clin. Endocrinol. 25: 1529, 1965. 2. Hung, W., Randolph, J. G., Sabatini, D., and Winship, T.: Lingual and sublinguM thyroid glands in euthyroid children, Pediafrics 38: 647, 1966, 3. Greig, W. R., Henderson, H. S., Boyle, J. A., McGirr, E. M., and Hutchison, J. H.: Thyroid dysgenesis in two pairs of monozygotie twins and in a mother and child, J. Clin. Endocrinol. 26: 1309, 1966. 4. Odell, W. D., Wilber, J, F., and Paul, W. E.: Radioimmunoassay of thyrotropin in human serum, J. Clin. Endocrinol. 25: 1179, 1965. 5. Spencer-Pent, J., Daly, J. R., and Smith, V.: A simple method for improving the specificity of the fluorimetric determination of adrenal corticosteroids in human plasma, J. Endocr~nol. 3 h 235, 1965. 6. Glick, S. M., Roth, J., Yalow, R. S., and Berson, S. A.: Immunoassay of human growth hormone in plasma, Nature (London) 199: 784, 1963. 7. Kulin, H. E., Rifkind, A., Ross, G. T., and Odell, W. D.: Total gonadotropin activity in the urine of prepubertal children, J. CIin. Endocrinol. In press. 8. Kohler, P. O., O'Malley, B. W., Rayford, P. L., Lipsett, M. B., and OdeIl, W. D.:

9. 10.

11. 12.


14. 15. 16. 17. 18.

Effect of pyrogen on pituitary trophic hormones, J. Clin. Endocrinol. 27: 219, 1967. Fisher, R. L., and DiChiro, G.: The small sella turcica, Am. J. Roentgenol. 91: 996, 1964. Costa, A., Cottino, F., Dellepicine, M., Ferraris, G. N., Lenart, L., Magro, G., Patrito, G., and Zuppett, G.: Thyroid function and thyrotropin activity in mother and fetus, in Cassano, C., and Andreoli, M., editors: Current topics in thyroid research, New York, 1965, Academic Press, Inc., p. 738. Rosen, F., and Ezrin, C. : Embryology of the thyrotroph, J. Clin. EndocrinoI. 26: 1343, 1966. Shepard, T. H.: Onset of function in the human fetal thyroid: Biochemical and radioautographic studies from organ euhures, J. Pediat. 69: 942, 1966 (abst.). Beam, J. G.: The role of the foetal pituitary in the development and growth of the foetal thyroid of the rabbit, J. Endoerinol. 36: 213, 1966. Johnson, J. E., Jr., and Johnson, D. E.: The lingual ectopic thyroid, Texas J. IVied. 58: 815, 1962. Steffen, E.: The ectopic thyroid gland, Am. Surg. 30: 267, 1964. Andersen, H, J.: Studies of hypothyroidism in children, Acta paediat. (Stockholm) 50: 50, 1961 (Suppl. 125). Gabr, M.: The role of thyroid dysgenesis and maldescent in the etiology of sporadic cretinism, J, P~mAT. 60: 830, 1962. Odell, W. D., Wilber, J., and Utiger, R. D.: Studies of thyrotropin physiology by means of radioimmunoassay, Recent Prog. Hormone Res. 23: 1967. In press.