Med. J. Cairo Univ., Vol. 62, No. 3, September: 677 - 682, 1994

Somatostatin and C-Peptide in Dysfunctions

MOHAMMAD A. ABDEL HAFEZ, M.D.; NAHED ABDEL GHANY, M.D.; SHERIF M. NAGUIB, M.D.; NAGUA E. SOBHY, M.D. and MOHAMMAD S. MOGAWER, M.D. The Departments of Medical Biochemistry and Internal Medicine, Faculty of of Medicine, Cairo University.

Abstract

Three groups of subjects were chosen; 20 patients with primary hypothyroidism, 20 patients with primary hyperthyroidism and a third group of 15 euthyroid subjects as a control group. Plasma , gastrin and C-peptide were determined in both fasting and lh postprandial after standard oral glucose load. FT3, FT4, TSH, oral glucose tolerance curve, serum cholesterol and triglycerides were also determined. It was found that both basal and stimulated somatostatin plasma concentrations were el- evated in hypothyroidism and diminished in hyperthyroidism. On the contrary, serum gastrin and C-peptide were decreased. Elevated somatostatin level in hypothyroidism has an inhibitory effect on gastrin and C-peptide. C-peptide was elevated in hyper- thyroidism, however glucose intolerance was noticed in only 20% of these subjects. Elevated gastrin level in hyperthyroidism suggests a role for gastrointestinal distur- bances observed in these patients.

Introduction had shown that somatostatin inhibits the hepatic T4 deiodenase, thus promoting its SOMATOSTATIN was first isolated from conversion to rTg rather than T3. the and was subsequently found in large amounts in endocrine cells This study was done to investigate the of the , and thyroid gland level of somatostatin as well as gastrin and Ill. It has a profound inhibitory effect on C-peptide in hypo and hyperthyroidism to growth (GH) secretion as well as clarify their role in these clinical situations. many other , including TSH, in- Subjects and Methods sulin, , gastrin, and va- soactive intestinal polypeptide @I. Soma- The study was carried out on 20 pa- tostatin infusion is known to inhibit tients with hyperthyroidism (13 females triiodothyronine (T3) and thyroxine (T4) and 7 males) and 20 patients with hypothy- release [31. Gavin and Moeller in 1983 [3,41 roidism (13 females and 7 males) as well

677 678 Mohammad A. Abdel Hafez, et al. as 15 euthyroid subjects as control group poration (DPC, Los Angeles CA). Serum (8 males and 7 females). The mean age for glucose was estimated by glucose oxidase the studied groups was 39.W14.22 y for method [9], kits were supplied by Biomer- the first, 39.50+16.52 y for the second and ieux (Cedex, France). 30.13k12.96 y for the third group mspec- tively. All participants were subjected to full history, thorough medical examination, Results routine laboratory investigations as well as The results are shown in tables 1 & 2. oral glucose tolerance curves, serum cho- lesterol and triglycerides. None of the par- Somatostatin (basal and stimulated) ticipants suffered form diabetes mellitus, showed a significant increase (p

Somatostatin pg/me Gastrin pg/ml C-peptide mmol/L Euthyroid group B. 19.95k2.92 152.OQ28.16 3.32kO.96 (n=15) S. 30.21+3.17 173.75~b39.20 5.28zb1.62 Hyperthyroid B. 13.76f5.67 166.25k59.81 3.62Lz1.28 group (n=2U) S 23.66k7.01 194.16k65.29 5.79f1.98 PtB. <0.005 >0.05 20.05 S. 0.05 >0.05 Hypothyroid group B. 3 1.25f6.59 127.3OLz20.06 2.63f0.79 (n=20) S. 46.65f7.29 149.6U29.61 4.01+_1 Pt B. 10.001 10.02 10.05 c 10.001 >0.05 10.025 h; B ‘;. io.001 10.05 CO.025 --_. --_ _~ l_-_-_-~ - <0.05 10.05 ~.

Tame (2): FTj, FI 3, TSH, Fasting and postprandial Serum glucose, Cholesterol and Triglycerides in the Investigated groups (Mean?SD).

FT3 FT4 TSH Plasma glucoste mg/dl Cholesterol Triglycer- pmol/L pmolL mU/L Fasting 30 min 60 min 90 min 120 min mg/dl ides gm/dl

Euthyroid group 6.73+ 14.%x+ 2.98+ 85.93+ 100.6+ 127.13+ 113.7M 95.27+ 194.6f 95.27f (n=15) 1.47 6.35 1.35 9.57 9.57 13.25 12.46 8.82 95.27 22.34 Hyperthyroid !8 ‘;(K 56k 0.22 99.3f 123.9jf 169.57f 141.34+ 118.W 221.25+ 89.75+ group (n=20) !?.bL 17.62 0.14 10.94 15.98 22.34 22.34 15.69 62.17 27.61 Pl Lii.001

Ingbar [121proposed that somatontatin bined action of somatostatin on both en- may be elevated as a result of the net result zymes could not be nullified. Further work of inhibited both secretion and catabolism is required to clarify the exact role of som- if the inhibition being exerted more on ca- atostatin on peripheral deiodination of T4. tabolism. However. in this work TSH was found to be elevated in hypothyroidism, in- The inhibited cause a spite of the presence of high level of soma- feedback rise in the TSH secretion which is probably not inhibited by somatostatin, tostatin in response to oral glucose load (as a monitor to somatostatin secretory re- TSH secretion in response to TRH is en- hanced and TRH stimulates GH secretion sponse) . only in hypothyroidism (not in the euthyr- The interrelationship between somatos- oid state). GH secretion is actually im- tatin, T3, T4 and TSH should be elucidated paired in response to many stimuli in hypo- to speculate another interpretation. Soma- thyroidism but TSH secretion is increased tostatin is incorporated in the hypothalamic 1161. control of TSH and GH secretion and it in- Somatostatin has many interactions hibits their secretion in a feedback manner. with other hormones and other regulatory This action of somatostatin as suggested by systems of the body. Also there is a diffe- Dhillon et al. [13] is a local inhibitory neu- rential inhibitory action of somatostatin on roendocrine hormone by the paracrine cells other hormones according to the endoge- related to the hypothyroid state. This was nous plasma level of somatostatin. There confirmed by De Rossa et al. [141 who are different types of somatostatin recep- demonstrated that somatostatin infusion tors in different tissues and post- does not influence TSH in normal subjects. effects of other hormones on somatostatin However, long term somatostatin infusion secretion have been reported t171. in hyperthyroid subjects reduces total T3 and free T3 and produced marked rise in We observed impaired glucose toler- rT3 suggesting stimulated extrathyroidal ance, not diabetes mellitus in 5 out of 20 deiodination effect of somatostatin on T4 hyperthyroid cases and the mean levels of converting it to the physiologically inac- plasma glucose at 60 and 90 minutes were tive form, rT3. significantly elevated in comparison to the euthyroid cases. C-peptide level was ele- Furthermore, somatostatin analogue ad- vated in the hyperthyroid cases, however ministration is an effective treatment for when compared with the level in the eu- patients with neoplastic inappropriate se- thyroid cases there was no significant dif- cretion of TSH [El. ference. Glucose metabolism is disturbed The findings of the present work suggest in thyroid disorders and impaired glucose that somatostatin elevation has not only an tolerance is recognised in thyrotoxicosis action on the thyroid cells to inhibit their se- Dal. cretory function, but also it may interfere, Many workers reported controversial somehow, with T4, S-deiodenase that con- results concerning plasma insulin concen- verts T4 to T3 in peripheral tissues. Alter- trations in thyroid disease 1191. natively, somatostatin might stimulate T 5- deiodenase activity, so that it promotes T4 Share et al. [ill demonstrated that som- conversion to rT3 rather than T3. Com- atostatin as well as insulin plasma levels Thyroid Dysfunction 681 are increased in hypothyroidism and re- for these results, plasma somatostatin de- duced in hyperthyroidism. They concluded termination will be useful in the follow up that the feedback regulation between islet of medullary carcinoma and somatostatino- cell hormones (glucagon, insulin and som- ma, considering the patient’s thyroid state atostatin) cannot explain these findings in whether hypothyroid or hyperthyroid be- thyroid disorders and suggested that a com- fore suspecting recurrence. Also somatos- mon metabolism (altered metabolic clear- tatin may be considered in pregnant hyper- ance rate) governs the level of these hor- thyroid patients specially when surgery mones in thyroid disorders. However, they and antithyroid treatment are risky. Moreo- found that glucagon was not significantly ver, thyroid functional state should be fol- changed, if this was the sole underlying lowed up in patients receiving somatostatin mechanism, plasma levels of glucagon analogues for any cause, as somatostatin would change simultaneously. may impair thyroid function as a whole, thyroid replacement may be considered A statistically negative correlation (r = when necessary. -0.~119 p < 0.065) was found between plasma glucose level and plasma somatos- References tatin level in the fasting state and at 1 hour 1. KRONHEIM, S.; BERELOWITZ, M. and postprandial in hypothyroidism as glucose PIMSTONE,B.L.: A radioimmunossay for stimulates somatostatin secretion. It may release inhibiting hor- be attributed to the inhibitory effect of mone: Method and quantitative tissue distri- somatostatin on glucose level either direct- bution. Clin. Endocrinol. 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