Oxymetholone

The pituitary gland is a hormone-responsive gland and is known to vary in size depending on the hormonal status of the patient and the multifaceted positive and negative feedback hypothalamic-pituitary-gonadal axis. Partial empty sells syndrome with an atrophied pituitary gland is seen in primary neuroendocrino-- pathies such as growth hormone deficiency, primary hypothyroidism, central diabetes insipidus and hypogonadism. Partial empty sells has also been shown to occur in patients with elevations in intracranial pressure. Secondary partial empty sells syndrome with significant pituitary gland atrophy from negative feedback inhibition of long-term exogenous hormonal use has not been previously reported. We are reporting on a case of partial empty sells syndrome occurring in an elite bodybuilder with a long history of exogenous abuse of growth hormone, testosterone and thyroid hormone. The pathophysiological mechanisms of secondary partial empty sells syndrome from exogenous hormone use and the possibility for elevations in intracranial pressure contributing to this syndrome will be discussed. [Neurol Res 2001; 23: 336-338]

Keywords: Anabolic steroids; axis; negative feedback; hormones; intracranial pressure; weightlifting

INTRODUCTION

The hypothalamic-pituitary-gonadal axis has both a positive and negative feedback system, which exerts control in the daily hormonal milieu. The pituitary gland will change in size depending on the hormonal demands of the patient, i.e. puberty, pregnancy or post-menopausal1. Partial empty sella syndrome is a result of pituitary gland involution which can occur secondary to a multitude of factors including elevated intracranial pressure, growth hormone deficiency, pituitary adenoma necrosis and a variety of developmental neuroendocrinopathies2-5. Age-related pituitary involution has been shown to occur in both sexes5. A magnetic resonance imaging study analyzing the sella turcica in 500 consecutive patients found a progressive increase in primary partial empty sella associated with aging, specifically the increase being more prominent in the fifth decade for females and sixth decade for males6. This age-related pituitary involution was thought to be a normal paraphysiologic variant. There are no reports on secondary partial empty sella syndrome occurring secondary to negative feedback from exogenous hormone replacement. We present a case of partial empty sella syndrome occurring in a healthy 39-year-old male elite bodybuilder secondary to negative feedback from long-term self-administration of multiple hormones. The neuroendocrinology of pituitary involution secondary to exogenous hormone use and other possible contributing factors will be discussed herein.

CASE REPORT

A 39-year-old male competitive bodybuilder, 5'11", 285 lbs, was being seen by the urology service for infertility and upon documenting a high normal prolactin level 11 ng ml ^sup -1^ (range 1-11 (mu)g l ^sup -1^) was referred to the neurosurgery service to rule out a possible prolactinoma. The patient has been in competitive bodybuilding for the past 20 years, with an intensive weightlifting workout of 90 min per day, 5 days per week. The patient history revealed a 17-year history of intermittent anabolic steroid use, with continuous use for the past four years. He also admitted to self-administration of growth hormone and thyroid hormone for the past two years. The patient's only complaint was infertility and he denied any physical symptoms or deficits. The patient had a normal developmental cascade reaching puberty at age 12. The patient denied any sexual dysfunction prior to anabolic steroid use, which began around 22 years of age. He admitted to an increased libido while on the anabolic steroids and denied any erectile, ejaculatory or sexual dysfunction while on or off the anabolic steroids. The patient and his spouse recently decided on building a family. After 18 months of unsuccessful attempts for pregnancy, the patient decided to be evaluated for possible infertility. Current medications: ibuprofen 200 mg bid prn joint pain. Illicit ergogenic aids included: four anabolic steroids-testosterone enanthate 600 mg im g weeks, oxymetholone 25 mg po qd, nandrolone decanoate 400 mg q week, methandrostenolone 30 po qd. Humatrope (growth hormone 8 iu sc q cl, cytomel (T3, thyroid hormone) 25 mcg po qd. Physical examination revealed an extremely muscular male, with symmetrical skeletal muscle hypertrophy. The patient's complete examination was normal including no breast development, gynecomastia or expressable discharge from the nipples. Testicles were descended bilaterally without palpable masses or marked atrophy. Neurologically the patient was intact with normal visual fields, no field cuts with fundoscopically sharp disc margins. Fasting laboratory values were significant for elevated testosterone 26 ng ml ^sup -1^ (range 3-10 ng ml ^sup -1^) and thyroid hormone T3 192 ni dl ^sup -1^ (75-170 ng dl ^sup -1^). Free thyroxine (FT4) 0.8 ng dl ^sup -1^ (0.9-1.6 ng dl ^sup -1^) and T4 4.0,(mu)g dl ^sup -1^ (4.511.0 (mu)g dl ^sup -1^) were both suppressed. Growth hormone 4.1 ng ml ^sup -1^ and insulin-like growth factor (IGF-1) 1.0u ml ^sup -1^ (0.30-1.4u ml ^sup -1^) were both within the normal range. TSH, LH and FSH were all undetectable. Due to the patient's body mass an open magnetic resonance image (MRI) was performed on the brain with emphasis on the pituitary gland. The MRI revealed a partial empty sella with the atrophied gland lining the sella caudally. There was no mass effect or adenoma present. The gland was uniformly hyperintense, with CSF surrounding the gland superiorly (Figure 1).

DISCUSSION

Partial empty sella syndrome secondary to exogenous hormone use has not been previously reported. Previous reports have demonstrated that testosterone can inhibit the hypothalamic-pituitary axis and that the pituitary will atrophy or hypertrophy depending on the hormonal demands of the patient1,7 . While partial empty sella can occur as a normal paraphysiologic variant in up to 9% of the population, the etiologies for this condition are multivariate, including age-related pituitary involution, elevated intracranial pressure, hormonal status and idiopathic to name a few1-8. There are two case reports on empty sella occurring secondary to high-dose corticosteroid pulse therapy for the treatment of nephrotic syndrome and lupus9,10. Interestingly both cases noticed subclinical deficiencies in growth hormone leading the authors to propose a direct feedback inhibition on the pituitary somatotrophs by corticosteroids. In addition the authors presented the analogy of corticosteroid-induced global cerebral atrophy as a similar mechanism for empty sella associated with corticosteroids11,12. We propose a direct feedback inhibition on the pituitary somatotrophs, gonadotrophs and thyrotrophs by exogenous hormone replacement therapy leading to pituitary atrophy and subsequent partial empty sella.

An additional interest in this case is the subject's 20year history of competitive bodybuilding and intense resistance-training workouts. Power athletes routinely use the Valsalva maneuver during weight-lifting which is known to provide a stabilizing force in the lumbar spine 13. This Valsalva maneuver increases intraabdominal and intra-thoracic pressure leading to increases in arterial pressure 14. Arterial pressures of 450/380 mmHg have been recorded in subjects during maximal weightlifting15. These supraphysiological arterial pressures last only 3-5 sec but can induce pathophysiologic changes within the cardiovascular system16. The elevations in intra-abdominal and intrathoracic pressure can also induce pathologic sequelae8,17 . While there are several case reports on catastrophic brain injury occurring with weightlifting, no studies have documented the intracranial pressure changes that may occur with maximal resistance-- training 18-20. We recently reported on pathological intra-ocular pressures and decreases in middle cerebral artery blood flow velocity occurring in power athletes during maximal weightlifting 14,21. Since intra-ocular pressure is an indirect measure of intracranial pressure, it is possible that the elevations in intracranial pressure experienced by this athlete in his daily weightlifting routine for approximately 20 years could lead to a cumulative effect causing a pressure-overload induced pituitary involution similar to that seen in idiopathic intracranial hypertension2,21,22.

While the exact etiology of partial empty sella syndrome in this patient may not be elucidated, we have offered two new plausible mechanisms:

1. Negative feedback induced pituitary atrophy from exogenous hormone use;

2. Intermittent elevations in intracranial pressure occurring with weightlifting causing a pressure-- overload induced pituitary involution.

We recommend a pituitary imaging study in a large number of patients on multiple hormone-replacement therapies and on a subset of veteran weightlifters to determine the incidence of secondary partial empty sella syndrome.

REFERENCES

1 Scheithauer BW, Sano T, Kovacs KT, Young WF, Ryan N, Randall RV. The pituitary gland in pregnancy: A clinicopathologic and immunohistochemical study of 69 cases. Mayo Clin Proc 1990; 65: 461-474

2 Kulali A, Baykut L, Wild K. Relationship between chronic raised intracranial pressure and empty sells presenting hormonal disturbances. Neurol Res 1990; 12: 99-102

3 Pocecco M, de Campo C, Marinoni S, Tommasini G, Basso T, Muzzolini C, Sacher B. High frequency of empty sells syndrome in children with growth hormone deficiency. Helv Paediatr Acta 1989; 4: 295-301

4 Keyaki A, Makita Y, Nabeshima S, Motomochi M, Itagaki T, Tei T. Secondary empty sells syndrome: Report of three cases and review of the literature. No Shinkei Geka 1982; 10: 1189-1194

5 Akcurin S, Ocal G, Berberoglu M, Memioglu N. Association of empty sells and neuroendocrine disorders in childhood. Acta Paediatr Jpn 1995; 37: 347-351

6 Foresti M, Guidali A, Susanna P. Primary empty sells. Incidence in 500 asymptomatic subjects examined with magnetic resonance. Radio/ Med 1991; 81: 803-807

7 Hande RJ, Burgess LH, Kerr JE, O'Keefe JA. Gonadal steroid

hormone receptors and sex differences in the hypothalamopituitary-adrenal axis. Horm Behav 1994; 28: 464-476

8 Dickerman RD, McConathy WJ, Smith AB. The pathogenesis of sliding hiatal hernias: Pressure overload? Clin J Gastro 1997; 25: 352-353

9 Kamoda T, Nakahara C, Matsui A. A case of empty sella after steroid pulse therapy for nephrotic syndrome. J Rheumatol 1998; 25:822-823

10 Kobayashi S, Warabi H, Hashimoto H. Hypopituitarism with empty sella after steroid pulse therapy. J Rheumatol 1997; 24: 236-238

11 Spiegel W, McGeady SJ, Mansmann HC. Cerebral cortical atrophy and central nervous system symptoms in a steroid-treated child with asthma. J Allergy Clin Immunol 1992; 89: 918-922

12 Benson J, Reza M, Winter J. Steroids and apparent cerebral atrophy on computed tomography scans. J Comput Assist

Tomogr 1978; 2: 16-23

13 Hamilton WF, Woodbury RA, Harper HT. Arterial cerebrospinal and venous pressures in man during cough and strain. AmJ Physiol 1944;141:42-50

14 Macdougall JD, Tuxen D, Sutton JR. Arterial pressure response to heavy resistance exercise. J Appl Phys 1985; 58: 785-789

15 Dickerman RD, Smith G, McConathy WJ, Roof LL, East JW, Smith AB. Intraocular pressure changes during maximal isometric contraction: Does this reflect retinal venous pressure or intracranial pressure. Neurol Res 1999; 21: 243-246

16 Dickerman RD, Schaller F, Zachariah NY, McConathy WJ. Left ventricular wall thickening does occur in power athletes with or without anabolic steroid use. Cardiol 1998; 90: 145-148

17 Smith AB, Dickerman RD, McGuirre S, East JE, McConathy WJ, Pearson F. Pressure-overload induced sliding hiatal hernias in resistance trained athletes. Clin J Gastro 1999; 28: 352-354

18 Kennedy MC, Corrigan AB, Pilbeam ST. Myocardial infarction and cerebral hemorrhage in a young bodybuilder taking anabolic steroids. Aust NZ J Med 1993; 23: 713

19 Haykowsky MJ, Findlay JM, Ignaszewski AP. Aneurysmal subarachnoid hemorrhage associated with weight training: Three case reports. Clin J Sport Med 1996; 6: 52-55

20 Frankle MA, Eichberg R, Zachariah SB. Anabolic androgenic steroids and a stroke in an athlete: Case report. Arch Phys Med Rehab 1988; 69: 632-633

21 Dickerman RD, Smith GH, East JW, McConathy WJ, Rudder L. Middle cerebral artery blood flow velocity during maximal weightlifting in elite power athletes. Neurol Res 2000; 22: 337-340

22 Aueong KG, Harliharan S, Chua EC, Leong S, Wong MC, Tsung PF, Yong VH. Idiopathic intracranial hypertension, empty sella turcica and polycystic ovary syndrome: A case report. Sing Med 1997; 38: 129-130

Rob D. Dickerman and Sivakumar Jaikumar

National Institutes of Neurological Disorders and Stroke, National Institutes of Health, Surgical Neurology Branch, Bethesda, MD, USA

Correspondence and reprint requests to: Rob D. Dickerman, DO, PhD, Long Island Jewish Medical Center, Department of Surgery, Division of Neurosurgery, 270-05 76th Avenue, New Hyde Park, New York, NY 11042, USA. [drrdd@yahoo.com] Accepted for publication September 2000.

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