Alvin B. Hayles

C-cell disease of the thyroid gland in multiple endocrine neoplasia, type 2b.

Multiple endocrine neoplasia, type 2b (MEN 2b) is a disorder characterized by C‐cell disease of the thyroid gland (medullary carcinoma or C‐cell hyperplasia, or both), pheochromocytoma, ganglioneuromatosis, and skeletal and connective tissue abnormalities. The medullary thyroid carcinoma (MTC) is bilateral and multicentric; it metastasizes locally and distally, often before the disease is recognized. Histologically proven C‐cell disease was present in 89 of the 107 patients (83%) reported with the condition, including 17 Mayo Clinic patients (average age at diagnosis, 19.2 years). Nineteen of the 107 patients (18%) died of MTC (average age at death, 25.3 years); 9 (8%) succumbed to pheochromocytoma, 7 of these also having metastatic MTC; 13 (12%) died of other or unknown causes, but 2 of these had disseminated MTC as well; 29 (27%) survive with metastatic MTC; an additional 21 (20%) are alive, but concentrations of plasma immunoreactive calcitonin (iCT) have not been measured; 6 more (6%), 5 of whom had thyroidectomy before the age of 12 years, are alive with normal plasma concentrations of iCT; and the remaining 10 (9%) have been lost to follow‐up. Survival of patients with MEN 2b after operation was reduced when compared with that of a control population—80% versus 99% at 5 years and 50% versus 98% at 10 years. The only effective treatment for MTC is total thyroidectomy before metastasis occurs. “Cure” of MTC in patients with MEN 2b has generally been obtained in those having total thyroidectomy before age 12. Therefore, in young patients suspected of having MEN 2b, we recommend prompt evaluation of C‐cell function by measurement of stimulated concentrations of iCT and treatment by total thyroidectomy if results are abnormal.

Childhood Cushing disease: results of bilateral adrenalectomy.

In view of the published reports of the successful correction of hypercortisolism in adult patients with Cushing disease by external pituitary irradiation and transsphenoidal pituitary microsurgery, leaving the patients with intact pituitary and adrenocortical function, we have reviewed the results of adrenalectomy in childhood Cushing disease seen at the Mayo Clinic. Twenty-seven patients were treated with total (16 patients) or subtotal (11 patients) bilateral adrenalectomy before the age of 20 years. Follow-up ranged from one to 27 years. Although hypercortisolism was corrected in all but one patient, 12 (45%) patients had roentgenographic evidence of a pituitary tumor and six (22%) of these required pituitary surgery. An additional six patients (22%) were pigmented, but had no abnormality on roentgenographic studies. The remaining nine patients (33%) were well, without evidence of pituitary tumor. We conclude that alternate forms of therapy should be considered for childhood Cushing disease.

Ovarian and parovarian tumors in infants and children.

Abstract A review of the literature on ovarian tumors in infants and children and 53 such cases from the Mayo Clinic are reported. In the new series, 50 of the tumors arose primarily in the ovary and 3 were metastatic; 29 of the 50 primary tumors were considered to be benign and 21 were clinically or histologically malignant. The over-all mortality rate in this series was 26 per cent.

Lymphocytic thyroiditis in children

The findings in the cases of 27 children with lymphocytic thyroiditis are summarized. A presumptive diagnosis was made on the basis of history and physical examination and was established by needle biopsy. Administration of thyroid hormone is an effective means of treatment if continued indefinitely. The patients in this series have progressed satisfactorily during the period of observation.

Thyroid disease among children with Down's syndrome (mongolism)

Observations on two mongoloid children, one having primary hypothyroidism and the other having primary hyperthyroidism, have been reported. Primary hypothyroidism in the mongoloid child, in each of the three cases reported to date, has been associated with uterine bleeding attributed to hormonal overlap in the pituitary feedback mechanism. The significance of this phenomenon is not clean. A total of sixteen cases of mongolism with hyperthyroidism have been described. There is no evidence that altered thyroid function plays a role in the clinical manifestations of mongolism, and significant alteration in thyroid function is uncommon among such patients. Both of the carrier protein systems responded to the stresses of the superimposed disease processes in these mongoloid children as they do in normal children. Specifically, the values for the erythrocytic uptake of 1-I131-triiodothyronine and thyroxine and the triiodothynonine binding capacities (Case 2 only) were all in the expected ranges for both thyroid derangements involved. Similarly, in Case 2, where an iron-deficiency anemia was also present, the increase in the iron binding capacity and presumably in the level of transferrin was on the order of that to be expected for the degree of iron deficiency. The response to stress of both carrier protein systems in Down9s Syndrome suggests that protein synthesis of transferrin and TBG is normal.

Multisystem neuronal degeneration, hepatosplenomegaly, and adrenocortical deficiency associated with reduced tissue arachidonic acid

We studied two brothers with a previously unrecognized syndrome characterized by failure to thrive, visual loss resulting from retinitis pigmentosa, sensorineural hearing loss, mental retardation, distal progressive muscular atrophy, hepatosplenomegaly, and adrenocortical deficiency. Biopsied tissue showed a consistent reduction of arachidonic acid and other polyunsaturated fatty acids, but not of linoleic acid. Deranged metabolism and specifically a deficiency of polyunsaturated fatty acids, including arachidonic acid, may be involved.

Adrenal insufficiency in a female pseudohermaphrodite.

A 6-year-old female pseudohermaphrodite developed adrenal cortical insufficiency during infancy. Evidence derived from a study of this patient suggests that congenital adrenal cortical hyperplasia was the cause of the pseudohermaphroditism. The cause of the subsequent adrenal cortical atrophy is unknown.

Progress and the Little Gray Pill

The superiority of synthetic levothyroxine sodium over thyroid extracts in the treatment of hypothyroidism seems established. The exciting developments in our understanding of thyroid physiology during recent years must parallel the excitement that accompanied the first demonstration of the effective control of hypothyroidism by the use of extracts from animal thyroid glands. Those of us who have witnessed some of these advances remember the excitement that they produced, and we have enjoyed and appreciated the advantages that they have provided. Progress is always rewarding, and I agree with Penny and Frasier (p 16) that synthetic levothyroxine is the drug of choice in the treatment of hypothyroidism in the year 1979. However, I am compelled to add a word in defense of an old and reliable friend, namely, the little gray pill of USP desiccated thyroid. To do less would seem unjust. For many years, I have prescribed levothyroxine for my