Ivor M. D. Jackson

Thyrotropin-Releasing Hormone

The modern era of neuroendocrinology was ushered in just over a decade ago with the isolation and characterization, from ovine1 and porcine2 hypothalamic tissue, of a tripeptide (pyroglutamyl-histi...

Treatment of Resistant Acromegaly with a Long-Acting Somatostatin Analogue (SMS 201-995)

Six patients with resistant acromegaly were given a long-acting somatostatin analogue (SMS 201-995) for 5 to 12 months. The clinical response was dramatic; relief of headache occurred within minutes of the injection. The mean 24-hour growth hormone levels fell acutely after the administration of 50 or 100 micrograms every 12 hours, especially in four patients with small tumors (p less than 0.001). Dosages of up to 1500 micrograms/d were necessary to produce maximum lowering of growth hormone secretion in some patients. On long-term treatment, plasma somatomedin-C levels fell in all patients and became normal in four. Plasma immunoreactive levels of SMS 201-995 related inversely to growth hormone concentration: A reproducible threshold for growth hormone inhibition in five of the patients, ranging from 70 to 1200 pg/mL, was maintained for 6 to 8 hours after the injections. This somatostatin analogue is effective in the treatment of acromegaly, has no major side effects, and causes only transient changes in carbohydrate metabolism.

xROLE OF GAMMA KNIFE THERAPY IN THE MANAGEMENT OF PITUITARY TUMORS

1. Gamma knife therapy is an effective method of delivering radiation to pituitary tumors that have failed surgery and may be used as primary treatment in circumstances in which the patient refuses or is unsuitable for a transsphenoidal procedure. 2. Stereotactic radiosurgery with the gamma knife unit is generally administered in a single session unlike fractionated radiotherapy, which is administered four to five times per week over a 6-week period. 3. Preliminary data suggest that resolution of pituitary hypersecretion is faster with gamma knife therapy than with conventional radiotherapy. 4. Because of the nature of the gamma knife therapy and the fact that the radiation dose conforms to the tumor shape, there is a steep fall-off of radiation to surrounding tissue. Accordingly, the radiation dose to extrapituitary brain is substantially less with gamma knife radiosurgery than with conventional radiotherapy. This suggests that the development of second brain tumors and neurocognitive complications, which are significant risks with conventional radiotherapy, is much less likely with gamma knife surgery. 5. Gamma knife radiosurgery can be used to ablate tumors invading the cavernous sinus. 6. Gamma knife radiosurgery is safe as long as the dose of radiation to the optic structures is kept under 10 Gy. 7. Long-term follow-up is required for pituitary tumors treated by gamma knife therapy so as to determine its efficacy as well as its effects on pituitary function and any resultant complications.

Familial Euthyroid Hyperthyroxinemia Resulting from Increased Thyroxine Binding to Thyroxine-Binding Prealbumin

MORE than 99 per cent of the thyroxine (T4) in blood is normally bound to specific plasma T4-binding proteins, including T4-binding globulin (TBG), T4-binding prealbumin (TBPA), and albumin.1 Howev...

Thyrotropin releasing hormone (TRH): Distribution in the brain, blood and urine of the rat

Abstract Measurement of thyrotropin releasing hormone (TRH) in the rat by a radioimmunoassay capable of detecting 6 pg is described. TRH was found in high concentration in the hypothalamus, especially in the stalk median eminence (SME). Small but significant concentrations were also detected hroughout the extrahypothalmic brain. Quantitatively, these levels are substantial, and suggest that this tripeptide may have an extrathyroidal brain function. TRH was measurable in the blood only in low concentrations, but large amounts were excreted in the urine (18.4ng/day).

Brain thyrotrophin-releasing hormone is independent of the hypothalamus.

THYROTROPHIN-releasing hormone (TRH) is widely distributed in regions of the brain outside the hypothalamus1–3, and behavioural4 and neurophysiological5 studies lend credence to the hypothesis1,6 that in these locations it is involved in neuro-transmission. To determine whether extrahypothalamic brain TRH arises from the hypothalamus or is synthesised in situ, we have made electrolytic lesions of the “thyrotrophic area”7 of the rat hypothalamus, and examined the effect on TRH content in the hypothalamus itself, the rest of the brain and the anterior and posterior pituitary. We have found that such lesions markedly reduce the hypothalamic content of TRH, deplete the pituitary gland of TRH and result in severe chemical hypothyroidism, but do not affect the large amount of TRH normally stored in the extrahypothalamic brain.

Thyroid Function in Down Syndrome.

The thyroid function of 181 patients with Down syndrome was investigated. When compared with a control group of 163 children we found T4 and FT4 levels to be significantly lower and T3 and TSH levels to be significantly higher in the Down syndrome population. Of the 181 patients with Down syndrome, 29 (16%) showed evidence of either uncompensated or compensated hypothyroidism: 11 (6%) had both low T4 and high TSH levels, 14 (8%) had only high TSH values, and 4 (2%) had only low T4 values. One of the patients with Down syndrome had a significantly elevated T4 level. Studying different age groups, we observed a decline of the mean T4, FT4, T3, FT3, and TBG values with advancing age. T4, T3, and TSH blood levels obtained in 1988 were slightly but not significantly lower when compared with values from 1985. Because thyroid dysfunctions in patients with Down syndrome are more common than in the general population, periodic thyroid hormone function tests should be performed in persons with Down syndrome in particular as they advance in age. Thus, individuals with significantly abnormal results can be identified early before clinical symptoms become manifest. If patients with Down syndrome are found to have a thyroid hormone disorder, appropriate treatment should be forthcoming, which in turn will enhance their quality of life.

The distribution of thyrotropin-releasing hormone (TRH) in the rhesus monkey spinal cord.

The distribution of thyrotropin-releasing hormone (TRH) in the Rhesus monkey spinal cord was studied using a highly specific antibody to TRH and the indirect peroxidase-antiperoxidase technique. TRH-positive fibers were found at all levels of the spinal cord and were in greatest concentration in the ventral gray, intermediolateral column and central gray. All motor nuclear groups in lamina IX of the ventral gray were innervated by TRH, frequently in close association with perikarya of alpha-motoneurons. The motor nuclei in the lumbar cord were the most heavily stained and contrasted to the minimal staining in the retrodorsolateral nuclear groups of the cervical, thoracic and sacral cord. Within the intermediolateral column, which contains the majority of preganglionic sympathetic neurons, TRH terminal fields reached their highest density between T2-T4 and T12-L2. Other preganglionic neurons including the nucleus intercalatus spinalis and the dorsal commissural nucleus were also densely innervated. These studies demonstrate the preferential distribution of TRH in the monkey spinal cord to regions containing alpha-motoneurons and preganglionic neurons and indicate that TRH may play an important role in the regulation of motor function and in the autonomic nervous system.

Amyotrophic lateral sclerosis Thyrotropin‐releasing hormone and histidyl proline diketopiperazine in the spinal cord and cerebrospinal fluid

In spinal cords from seven amyotrophic lateral sclerosis (ALS) patients and four controls, we found no difference in thyrotropin-releasing hormone (TRH) concentration relative to protein content, but there was a reduction per tissue wet weight in ALS. Immunohistochemical localization of TRH in ALS cord was unaltered. Histidyl proline diketopiperazine (HisPro-DKP), a possible metabolite of TRH, was significantly elevated per protein content in ALS. CSF levels of TRH and HisPro-DKP were unchanged. These findings suggest that TRH neurons are not primarily affected in ALS, but TRH and tissue protein are lost together as the disease progresses.

Why does anyone still use desiccated thyroid USP

The effect on thyroid status of changing from thyroid USP to sodium L-thyroxine was evaluated in 40 patients. With thyroid, abnormally high triiodothyronine (T3) levels were seen in 36 of 38 patients receiving doses of 90 to 240 mg; compared to sodium L-thyroxine, 0.15 to 0.2 mg, the serum T3 was higher (289 +/- 15 ng/dl versus 176 +/- 9 ng/dl, p less than 0.0005) and the thyroxine (T4) lower (7.4 +/- 0.3 microgram/dl versus 11.6 +/- 0.5 microgram/dl, P less than 0.01). Thyrotoxic symptoms occurred in six patients and diminished or disappeared after the change to sodium L-thyroxine, suggesting that the raised T3 level with thyroid may have undesirable effects in some patients. The T4 level, because it is low whether symptoms are present or not, may inadvertently suggest the need for higher dosage of desiccated thyroid in patients who have already received adequate replacement. The dose of sodium L-thyroxine was adequately assessed by measurement of both T4 and T3 levels. Thyroid USP should be discontinued as thyroid medication since it produces thyroid hormone levels that are misleading estimates of thyroid function and can cause thyrotoxic symptoms.