Summary
Endocrine functions were examined in 21 patients with mitochondrial myopathies presenting with chronic progressive external ophthalmoplegia and other additional neurological and multisystemic symptoms. Ten patients had the features of the Kearns-Sayre syndrome. Deletions of the mitochondrial DNA were found in 4 out of 5 patients examined. Fourteen patients, including 3 with deletions of the mitochondrial DNA, had various and often multiple endocrine abnormalities: 6 patients were of short stature, 3 had irregular menstrual cycles, 3 had undersized testicles, 5 showed an insufficient rise of growth hormone following the administration of growth-hormone-releasing hormone, 4 showed an insufficient rise in FSH after administration of gonadotropin-releasing hormone, 5 had manifest diabetes mellitus, 3 showed an impaired glucose tolerance, and 2 patients had subnormal serum levels of parathormone in combination with hypocalcaemia. One patient additionally had Klinefelter's syndrome with a kariotype 47, XXY and increased levels of FSH and LH, subnormal levels of testosterone and subnormal testicular volume. The occurrence of endocrine defects correlated with the duration of disease. The data demonstrate that endocrine abnormalities are frequently associated with mitochondrial myopathy, indicating that this multisystemic disease also involves various endocrine tissues.
Similar content being viewed by others
Abbreviations
- ACTH:
-
adrenocorticotropic hormone
- CoQ:
-
coenzyme Q10
- CRH:
-
corticotropin-releasing hormone
- FSH:
-
follicle-stimulating hormone
- GH:
-
growth hormone
- GHRH:
-
growth-hormone-releasing hormone
- GnRH:
-
gonadotropin-releasing hormone
- LH:
-
luteinizing hormone
- mtDNA:
-
mitochondrial DNA
- PTH:
-
parathormone
- TRH:
-
thyrotropin-releasing hormone
- TSH:
-
thyroid-stimulating hormone
- T3 :
-
triiodothyronine
- T4 :
-
thyroxine
References
Berenberg RA, Pellock JM, DiMauro S, Schotland DL, Bonilla E, Eastwood A, Hays A, Vicale CT, Behrens M, Chutorian A, Rowland LP (1977) Lumping or splitting? “Ophthalmoplegia-plus” or Kearns-Sayre syndrome? Ann Neurol 1:37–54
Boltshauser E, Jerusalem F, Niemeyer G, Huber C (1977) Kearns-Syndrom. Schweiz Med Wochenschr 107:1880–1888
Bremner WJ (1990) Pituitary gonadotropins and their disorders. In: Becker KL (ed) Principles and practice of endocrinology and metabolism. Lippincott, Philadelphia, pp 152–156
Croxson TS, Chapman WE, Miller LK, Levit CD, Senie R, Zumoff B (1989) Changes in the hypothalamic-pituitary-gonadal axis in human immunodeficiency virus-infected homosexual risen. J Clin Endocrinol Metab 68:317–321
Danta G, Hilton RC, Lynch PG (1975) Chronic progressive external ophthalmoplegia. Brain 98:473–492
Doriguzzi C, Palmucci L, Mongini T, Bresolin N, Bet L, Comi G, Lala R (1989) Endocrine involvement in mitochondrial encephalomyopathy with partial cytochrome c oxidase deficiency. J Neurol Neurosurg Psychiatry 52:122–125
Dufow DR, Gaskin JH, Jubiz WA (1990) Dynamic procedures in endocrinology. In: Becker KL (ed) Principles and practice of endocrinology and metabolism. Lippincott, Philadelphia, pp 1768–1769
Dufow DR, Gaskin JH, Jubis WA (1990) Endocrine drugs and values: dynamic procedures in endocrinology. In: Becker KL (ed) Principles and practice of endocrinology and metabolism. Lippincott, Philadelphia, pp 1772–1773
Gerbitz KD, Obermaier-Kusser B, Zierz S, Pongratz D, Müller-Höcker J, Lestienne P (1990) Mitochondrial myopathies: divergences of genetic deletions, biochemical defects and the clinical syndromes. J Neurol 237:5–10
Grünwald F, Zierz S, Broich K, Dewes W, Beker T, Biersack H-J (1991) Brain SPELT imaging with Tc-99m HMPAO in ophthalmoplegia plus. Clin Nucl Med 16:20–23
Holdsworth S, Atkins RC, de Kretser DM (1977) The pituitary-testicular axis in men with chronic renal failure. N Engl J Med 296:1245–1249
Horwitz SJ, Roessmann U (1978) Kearns-Sayre syndrome with hypoparathyroidism. Ann Neurol 3:513–518
Huenges R (1982) Secondary growth failure. Eur J Pediatr 139:230–238
Hung W (1990) Micropenis, hypospadia and cryptorchidism in infancy and childhood. In: Becker KL (ed) Principles and practice of endocrinology and metabolism. Lippincott, Philadelphia, pp 760–766
Kearns TP, Sayre GP (1958) Retinitis pigmentosa, external ophthalmoplegia, and complete heart block. Arch Ophthalmol 60:280–289
Lundberg PO (1966) Observations on endocrine function in ocular myopathy. Acta Neurol Scand 42:39–61
Pellock JM, Behrens M, Lewis L, Holub D, Carter S, Rowland LP (1978) Kearns-Sayre syndrome and hypoparathyroidism. Ann Neurol 3:455–458
Pfeifer MA, Halter JB, Porte D (1981) Insulin secretion in diabetes mellitus. Am J Med 70:570–588
Scully RE, Mark EJ, McNeely WF, McNeely BU (1987) Case records of the Massachusetts General Hospital: Case 34–1987. N Engl J Med 317:493–501
Shanske S, Moraes CT, Lombes A, Miranda AF, Bonilla E, Lewis P, Whelan MA, Ellsworth CA, DiMauro S (1990) Widespread tissue distribution of mitochondrial DNA deletions in Kearns-Sayre syndrome. Neurology 40:24–28
Simopoulos AP, Delea CS, Bartter FC (1971) Neurodegenerative disorders and hyperaldosteronism. J Pediatr 79:633–641
Smith SR, Chhetri MK, Johanson AJ, Radfar N, Migeon CJ (1975) The pituitary-gonadal axis in men with proteincalorie malnutrition. J Clin Endocrinol Metab 41:60–69
Tanabe Y, Miyamoto S, Kinoshita Y, Yamada K, Sasaki N, Makino E, Nakajima H (1988) Diabetes mellitus in Kearns-Sayre syndrome. Eur Neurol 28:34–38
Toppet M, Telerman-Toppet N, Szliwowski HB, Vainsel M, Coers C (1977) Oculocraniosomatic neuromuscular disease with hypoparathyroidism. Am J Dis Child 131:437–441
Vigersky RA, Chapman RM, Berenberg J, Glass AR (1982) Testicular dysfunction in untreated Hodgkin's disease. Am J Med 73:482–486
World Health Organisation (1980) Technical report, series no. 646. Second report diabetes mellitus. World Health Organisation, Geneva
Zeviani M, Gellera C, Pannacci M, Uziel G, Prelle A, Servidei S, DiDonato S (1990) Tissue distribution and transmission of mitochondrial DNA deletions in mitochondrial myopathies. Ann Neurol 28:94–97
Zeviani M, Moraes CT, DiMauro S, Nakase H, Bonilla E, Schon EA, Rowland LP (1988) Deletions of mitochondrial DNA in Kearns-Sayre syndrome. Neurology 38:1339–1346
Zierz S, Jahns G, Jerusalem F (1989) Coenzyme Q in serum and muscle of 5 patients with Kearns-Sayre syndrome and 12 patients with ophthalmoplegia plus. J Neurol 236:97–101
Zierz S, von Wersebe O, Gerbitz KD, Jerusalem F (1990) Ophthalmoplegia-plus: Klinische Variabilität, biochemische Defekte der mitochondrialen Atmungskette und Deletionen des mitochondrialen Genoms. Nervenarzt 61:332–339
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Quader, A., Zierz, S. & Klingmüller, D. Endocrine abnormalities in mitochondrial myopathy with external ophthalmoplegia. Clin Investig 70, 396–402 (1992). https://doi.org/10.1007/BF00235520
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00235520