Abstract. A syndrome of periodic catecholamine and prostaglandin E2 discharge is described in 2 patients aged 17 and 3 years. They had recurrent attacks of vomiting, hypertension and psychotic depression for several years with a fixed periodicity. At initiation of the attack, plasma ACTH, AVP, norepinephrine and prostaglandin E2 were markedly elevated, whereas dopamine was undetectable. This resulted in hypercortisolemia, hyponatremia and oliguria, which were completely normalized when the attack subsided. Dopaminergic inhibition by metoclopramide injection induced a sustained rise in plasma bicyclo-prostaglandin E2 in the patients, a transient rise in 4 controls, and no response in 8 control children. The 4 control responders had significantly higher plasma norepinephrine levels and aldosterone responses than the non-responders (P < 0.001). There was a linear correlation between peak values of bicyclo-prostaglandin E2 and basal norepinephrine levels (r = 0.990, P < 0.001). The patients released bicyclo-prostaglandin E2 and aldosterone more easily than the control responders in terms of plasma norepinephrine and dopamine levels. Treatment of the patient with clonidine was partially effective, whereas administration of indomethacin completely suppressed recurrence of the attacks for 1 year. These results suggest the etiologic possibility that the patients have a decreased dopaminergic inhibition of prostaglandin E2-mediated norepinephrine secretion, which causes periodic discharge of norepinephrine and concomitant release of ACTH and AVP.

Nine patients with athyrotic or ectopic cretinism ages 6 mo.-17 yrs-were studied to examine the relation between age and the quantities of oral L-thyroxine (T4) adequate to restore TSH hypersecretion to normal levels by feedback control. All but one patient had very low levels of endogenous T4 (below 1.0 mug/100 ml) before treatment. However, based on clinical signs and serum T4-1 values, all were judged to be euthyroid or sub-clinically hyperthyroid by L-T4 replacement during the observation period. L-T4 dosage was increased or decreased by 25 or 50 mug/day at 2-12 mo. intervals, and the TSH response to exogenous thyrotropin-releasing hormone (TRH) was tested sequentially at each dose of L-T4 until a normal or slightly suppressed TSH response was obtained The L-T4 dosage which was associated with normal TSH responsiveness to TRH (the adequate L-T4 dose) was high in infancy (10 mug/kg/day), decreasing with age to a level of 3-4 mug/kg/day in pubertal children (correlation coefficient r=-0.820, P less than 0.01). The adequate L-T4 dose observed between 4 and 12 yrs of age was lower than the usually recommended dose (4-6 vs. 7-8 mug/kg/day). On these L-T4 doses, serum T4I concentrations were significantly higher in patients under 5 yrs of age than in older patients (8.3+/-1.5 vs. 6.5+/-0.7 mug/100 ml, P less than 0.02). Serum triiodothyronine (T3) values were also elevated in young children, decreasing with age to the normal range. TSH responses to TRH were completely suppressed at the serum T4-I levels of 9 mug/100 ml and T3 of 250 ng/100 ml or less in 7 patients over 4 yrs of age, but not in 2 younger patients. Although the number of patients examined was limited, these results suggest that the pituitary threshold for feedback regulation of TSH secretion by T4 decreases with age in children with cretinism and the usually recommended replacement doses of L-T4 between 4 and 12 yrs of age are probably overestimated.

No abstract

Effects of hyper-and hypothyroidism on catecholamine (CA) metabolism in the brain, adrenal glands, liver, and brown adipose tissue (BAT) were studied in adult rats during cold acclimation. Hypothyroidism was induced by the administration of propylthiouracil (PTU) and hyperthyroidism by the injection of thyroxine (T4). After 2 weeks of treatment, they were exposed to cold (5\s=deg\C)and sacrificed after 1 or 4 weeks. Although the body weight gain of PTU-treated rats were markedly impaired, the body temperature was maintained within normal range. They had increased cerebral dopamine, adrenal CA and BAT norepinephrine (NE) contents, enhanced cerebral tyrosine hydroxylase and adrenal dopamine \g=b\-hydroxylase (DBH) activities and elevated [3H]dihydroalprenolol (DHA) binding to liver plasma membranes (P <0.01 vs controls). T4-treated rats showed an increased brain and adrenal CA only after cold exposure. The BAT NE content, DHA binding to liver plasma membranes, and[3H]guanosine diphosphate binding to BAT mitochondria were reduced by 30 to 50% from control values after 4 weeks of cold exposure. These results indicate that during cold acclimation, 1) thyroid hormone deficiency is associated with an accelerated CA synthesis and release, which results in an enhanced BAT thermogenesis, and 2) the hyperthyroid state suppresses CA release, hepatic DHA binding, and BAT heat production. Thus, there is a close metabolic interrelationship between thyroid hormone and CA during exposure to cold. CA appears to ameliorate thyroid hormone excess or deficiency.The calorigenic action of thyroid hormone and catecholamine (CA) is well established. Both arise from the common precursor, tyrosine, and play a pivotal role in the homeotherm. Thyroid hor¬ mone controls the basal metabolic rate (BMR) by stimulating oxydative phosphorylation of the mitochondrial respiratory chain. Thyroid hor¬ mone-induced changes in BMR usually occur slowly and tend to persist. On the other hand, CA increases heat production above BMR by enhanc¬ ing lipolysis and glycolysis in response to various metabolic demands, which are rapidly switched on and off. On exposure to cold, an elevation of heat pro¬ duction is brought about by the enhanced nore¬ pinephrine (NE) secretion from the sympathetic nervous system (Hsieh et al. 1957b), which is the underlying mechanism of non-shivering thermo¬ genesis. Recently, the major site of non-shivering thermogenesis is recognized to be brown adipose tissue (BAT) (Foster & Frydman 1978). Although a line of evidence indicates that cold exposure evokes a rapid rise in plasma thyrotropin (TSH) (Knigge 1960;Itoh et al. 1966) and a stimulation of thyroid secretion, the interrelationship be¬ tween thyroid hormone and CA still remains to be elucidated. In our study, we examined effects of altered thyroid states on the CA metabolism in the central nervous system (CNS), adrenal glands, liver, and BAT during cold acclimation. We show that there is a close metabolic interrelationship between thyroid hormone and CA.

An 8-yr-old girl is presented who had periodic attacks of vomiting, psychotic depression, drowsiness, and hypertension (160/110 mm Hg) for a period of 16 months after head injury. At the initiation of the attack, serum ACTH and vasopressin levels were prominently increased (610 pg/ml and 41 microunits/ml, respectively), followed by hypercortisolemia, hyponatremia, and hypoosmolality in plasma. Serum PRL also was elevated (91 ng/ml). Responses of GH and cortisol to insulin-induced hypoglycemia and those of TSH to TRH were reduced. Urinary excretion of epinephrine and norepinephrine were increased, while dopamine (DA) excretion was reciprocally decreased, resulting in a marked elevation of the epinephrine plus norepinephrine to DA ratio during the episodes (0.4-4.5); this was normalized on attack-free days (0.08-0.25). During the attack, the concentration of homovanillic acid, a major metabolite of DA in the brain, also was reduced in cerebrospinal fluids from 70 to 23 ng/ml. The administration of methyl-dopa and reserpine effectively suppressed the recurrence of the episode. Although the exact cause of this syndrome is unknown, a periodic metabolic dysfunction of catecholamine in the central nervous system might be postulated.