Testicular Germ Cell Tumour Presenting As Thyrotoxicosis
I read with interest the case report ‘Testicular germ cell tumour presenting as thyrotoxicosis’1 in this journal. The article is a timely reminder for laboratarians and clinicians about the myriad of thyrotoxic causes. Additional comments are warranted, however.
The basis for diagnosing any medical condition remains that of a thorough history, with a high index of suspicion, and clinical examination. The latter would have undoubtedly picked up the tumour size and site. It is perplexing that the patient is not aware of his 9 cm testicular size. This is equivalent to, if not larger than, the size of a tennis ball. It is true however that ‘the genitalia remain the graveyard of the diagnostically inept’.
There is no doubt that the patient is clinically thyrotoxic. When the patient has not improved, a review of the diagnosis is mandatory. Additional investigations, including elevated free tri- iodothyronine level, a positive thyroid ^sup 99m^technetium- pertechnetate uptake scan and negative auto-immune thyroid auto- antibody study, should assist in further delineating the diagnosis.2
The pathophysiology of human chorionic gonadotropin (hCG)- mediated thyrotoxicosis is the excess synthesis and subsequent release of thyroid hormones due to overwhelming thyrotropin (TSH)- receptor binding. Thus the thioamides, which act by blocking thyroid hormone synthesis, should work providing adequate dosage is used. Carbimazole of up to 60 mg daily has been used in similar situation.3,4 Also, extreme caution should be applied to the use of nonspecific beta-blockade drugs such as propranolol in the presence of worsening breathlessness, even in the absence of known and existing bronchospasm.
It is the β-subunits of hCG and TSH that share structural homology. There is 85% sequence homology in the first 114 amino acid sequence and 12 cysteine residues in the β-subunits. The α- subunit of HCG is identical to other pituitary glycoprotein hormones.5 It has been estimated that for every 10 000 IU/L hCG increase, there is 0.6 pmol/L increase in free tetraiodothyronine (fT4) and a 0.1 mIU/L decrease in TSH concentrations.6
The impression given that tumour markers (TMs) are used in an attempt to localize the site of the primary tumour should be dispelled. β-HCG is probably the only TM where high levels can assist in the diagnosis – but only in the right clinical context.7 Generally, TMs should remain a prognostic indicator and a monitoring tool in response to treatment.
It is not definitive that the patient dies from pulmonary- embolus related cause (tumour or thrombosis). It is critical that patients of this age group who die acutely of uncertain causes undergo a complete and thorough post-mortem examination. Understandably, the post-mortem is probably a limited one in this case. Such practice may give credence to family screening given that a proportion of germ cell tumours are hereditary in nature.8 An alternative to the above hypothetical cause of death is hyperthyroidism related heart failure exacerbating unrecognized ischaemic or hypertensive heart diseased.9 Thyroid storm is another consideration and is consistent with the clinical state. Death due to cardiac arrhythmia is unlikely as the frequency of ventricular asystole or arrhythmia in thyrotoxosis is similar to that of the general population. This lends support to the theory of probable coexisting coronary cardiac disease. Thyroid excess may also elicit potassium disturbance further aggravating cardiac arrhythmia albeit in genetically predisposed individuals.11
References
1 Tilbrook LK, Slater J and Blainey AD. Testicular germ cell tumour presenting as thyrotoxicosis. Ann Clin Biochem 2004; 41: 248- 9
2 Franklyn JA. The management of hyperthyroidism. N Eng J Med 1994; 331: 1731-8
3 http://www.mims.com.au (last cited 11/6/2004)
4 Chowdhury TA, Tanchel BM, Jaganathan RS, Dodson PM. A toxic testicle. Lancet 2000; 355: 2046
5 Cole LA. Immunoassay of human chorionic gonadotropin, its free subunits, and metabolites. Clinical Chemistry 1997; 43: 2233-43
6 Glinoer D. The regulation of thyroid function in pregnancy: Pathways of endocrine adaptation from physiology to pathology. Endocrine Reviews 1997; 18: 404-33
7 Norwich A, Huddart R, Deamsley D. Markers and management of germ-cell tumours of the testes. Lancet 1998; 352: 1535-8
8 Forman D, Oliver RTD, Brett AR, et al. Familial testicular cancer: a report of the UK family register, estimation of risk and an HLA Class 1 sib-pair analysis. Br J Cancer 1992; 65: 255-62
9 Klein I and Ojamaa K. Thyroid hormone and the cardiovascular system. N Eng J Med 2001; 344: 501-9
10 Osman F, Gammage MD, Sheppard MC and Franklyn JA. Cardiac dysrhythmias and thyroid dysfunction: the hidden menace. JCEM 2002; 87: 963-7
11 Tran HA, Kay SE, Rende M, Doery JCG, et al. Thyrotoxic, hypokalaemic periodic paralysis in Australasian men. Intern Med J 2003; 33: 91-4
Dr Huy A Tran
Department of Clinical Chemistry
Hunter Area Pathology Service
John Hunter Hospital
Newcastle 2310
NSW Australia
Copyright Royal Society of Medicine Press Ltd. Nov 2004