Adolf Kussmaul worked across the breadth of internal medicine as it was in the nineteenth century. He made important discoveries in psychology, neurology, pathology, and pathophysiology. This can be seen from his list of eponyms: Kussmaul breathing, Kussmaul's sign, Kussmaul disease (polyarteritis nodosa), Kussmaul coma (diabetic ketoacidosis), and Kussmaul's aphasia (selective mutism). He was the first to describe word blindness (dyslexia), polyarteritis nodosa, progressive bulbar paralysis, and mesenteric embolism, and was the first to perform gastric lavage, thoracentesis, esophagoscopy, and gastroscopy. Kussmaul made a careful study of a famous sword swallower and, by noting the position in which the sword swallower held his head, realized that it would be possible to introduce an inflexible tube through the esophagus and into the stomach. Kussmaul thus developed the first endoscope. He also developed the first ophthalmoscope. Adolf Kussmaul was one of the most creative minds in the history of medicine.
Marcello Malpighi supplied the final link in understanding the circulation of the blood. Galen described the four chambers of the heart and the connecting valves. In the article De pulmonibus, Malpighi described the anatomy of the frog lung, bronchioles, alveoli, and the pulmonary capillary bed. In these capillaries he could see, in vivo, red globules moving from arterioles to venules. The capillary bed was the final insight required to solidify the concept of the circulation of the blood. Malpighi's study of the liver, spleen, and kidney convinced him that organs are composed of glandular structures, corpuscles, that in aggregate, constitute the organ. He described the renal corpuscle, the splenic corpuscle, and the hepatic secretory unit. He also studied neuroanatomy and concluded that the brain is an endocrine organ. The last decade of Malpighi's life was accompanied by challenge and criticism as is often the case for scientific pioneers.
Richard Lower's scientific contributions can be thought of in three phases. The first was work done in association with Thomas Willis. Lower developed the metal syringes that allowed for the perfusion of the venous and arterial systems of the brain, and his skills with dissection of the brain were legendary. It was Lower who showed that ligation of three of the four arteries supplying the brain can be survived because of the collateral circulation provided by the circle of Willis. Dogma held that any fluid overload was managed by the ventricles of the brain and that normal fluid balance was maintained by the excretion of pituita, again expressed as nasal and pulmonary catarrh. Lower examined these concepts in detail, finding through careful dissection no pores connecting the nasal cavity with the pituitary gland or with the sella turcica.
It is not clear whether or not subclinical hypothyroidism (SH) is associated with an increased risk for cardiovascular disease.We prospectively examined 43 women with SH and 49 healthy controls of similar age.Fasting blood levels of thyrotropin, free thyroxin, antibodies to thyroid peroxidase and thyroglobulin, glucose, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, and insulin were measured. Body mass index, waist and hip circumferences, blood pressure, homeostasis model assessment 2-insulin resistance index, and the presence of metabolic syndrome (MS) were also evaluated.Mean systolic blood pressure was increased in SH patients versus controls (128.6 vs. 120.7 mm Hg; P = 0.04). Mean values of total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and insulin were not different in patients with SH compared with controls, SH had significantly higher triglyceride levels (1.50 +/- 0.65 mmol/L) and glucose levels (5.26 +/- 0.63 mmol/L) compared with controls (1.27 +/- 0.59, 5.05 +/- 0.52; P = 0.04, P = 0.04, respectively). Although body mass index values were similar in both groups, patients had greater waist circumference than controls (90.7 +/- 13 cm vs. 81.8 +/- 10.6; P = 0.0007). The percentages of patients with SH having hypertension (34.1%), hypertriglyceridemia (37.2%), hyperglycemia (20.9%), and greater waist circumference (51.2%) were higher than the percentages in controls. Thus, the percentage of MS in patients (41.5%) was significantly higher than in controls (12.2%; P = 0.003). SH had significantly higher likelihood of cardiovascular risks (odds ratio, 6.26; 95% confidence interval, 1.6-4.49; P = 0.008 for MS).We conclude that SH is associated with greater probability of MS. This may increase the risk of accelerated atherosclerosis and premature cardiovascular disease in these patients.
Oncogenic osteomalacia is a rare metabolic bone disorder characterized by hypophosphatemia, hyperphosphaturia, and low or inappropriately normal 1,25-dihydroxyvitamin D level. It is caused by phosphaturic factors secreted by mesenchymal tumors. Removal of these tumors can result in cure of the condition. However, the diagnosis is often delayed for months to years due to insufficient recognition of this disorder. One of the earliest clues to this diagnosis is the presence of hypophosphatemia. However, this may be ignored by the Unsuspecting clinician. We report a case of a man who presented with persistent pain in his knees, hips, and back. The diagnosis was delayed for 18 months, resulting in progression of disability to the point of difficulty with ambulation. Laboratory studies revealed hypophosphatemia. Following recognition of the disorder, the causative tumor was found in the right middle turbinate. Removal of the turner resulted in complete recovery. The differential diagnosis, diagnostic evaluation, localization of tumor, and treatments are discussed.
Hypoglycemia can occur as a complication during the treatment of diabetes mellitus. The potential neurologic consequences of severe hypoglycemia, including coma and seizure, are well-recognized. Less commonly considered are possible cardiovascular complications associated with hypoglycemia. Myocardial ischemia and infarction are known to occur in the setting of hypoglycemia. We describe 4 cases of hypoglycemia associated with silent myocardial infarction. We explore the mechanisms by which hypoglycemia or the medications used to treat diabetes increase the risk of myocardial infarction. We also discuss how the stress of a recent myocardial infarction can elevate the risk of severe hypoglycemia. In view of this potential association, diabetic patients should be monitored closely for these 2 complications occurring sequentially in close temporal proximity.
alpha-interferon and ribavirin are the drugs of choice for treating Hepatitis C, but may trigger thyroid disorders as a major complication. Several studies have shown a variation in the prevalence (1%-35%) of this association influenced by geographical distribution, genetics, and iodine intake of the population. The objective of this study was to analyze thyroid disorders in patients with hepatitis C in treatment or not with alpha-interferon and ribavirin. We evaluated the frequency and pattern of thyroid disorders in 25 patients with hepatitis C in treatment with alpha-interferon and ribavirin (G1), 62 patients with hepatitis C without treatment (G2) and 82 patients without hepatitis C (control group) measuring thyroid-stimulant hormone, antiperoxidase antibodies (anti-TPO), and anrtithyroglobulin (anti-TG). Hypothyroidism was more frequent in hepatitis C patients under treatment (36%), while the frequency of thyroid antibodies was not different in the 3 studied groups, respectively (12% in G1; 8.06% in G2, and 17.07% in control group). It was not possible to demonstrate the higher prevalence of autoimmune thyroid disease in hepatitis C carriers under treatment with alpha-interferon and ribavirin; even though hypothyroidism is more frequent in this group. Patients with hepatitis C treated with these medications should be screened for thyroid dysfunction.
Primary hyperparathyroidism is the most common cause of hypercalcemia in nonhospitalized patients. Recently, technetium-99m sestamibi (methoxyisobutylisonitrile, Tc-99m MIBI) imaging has been established as the best method for detecting a parathyroid adenoma. However, sestamibi accumulates in a number of nonparathyroid tissues. We report a patient with suspected primary hyperparathyroidism, who underwent sestamibi parathyroid imaging. In addition to sestamibi retention in a parathyroid adenoma, retention was observed in a breast fibroadenoma, which mimicked an ectopic parathyroid adenoma.
Journal of Occupational and Environmental Medicine: September 2004 - Volume 46 - Issue 9 - p 930
Aim: The aim is to describe a very rare case of idiopathic granulomatous hypophysitis presenting as panhypopituitarism on the background of chronic renal failure and type 2 diabetes mellitus. The patient presented with fatigue and episodes of self-terminated hypoglycemia (while on sulfonylurea) as the sole manifestation of panhypopituitarism. The case also highlights the difficulties of identifying patients with hypophysitis in the setting of chronic renal failure. Results: We describe a middle-aged man who presented to us with the sole complaints of early morning fatigue and hypoglycemia (while on glimepiride), with a background history of type 2 diabetes and chronic renal failure. Before visiting our practice, he was repeatedly evaluated for decompensation of renal and cardiovascular disease without much success. When we saw the patient there was no obvious evidence of any endocrine disturbance, especially as the blood pressure was high without any postural drop. It was only when the patient persistently complained of an impaired quality of life due to the fatigue that we decided to chase an endocrine cause for the same. On endocrine evaluation, we diagnosed panhypopituitarism secondary to idiopathic granulomatous hypophysitis. Conclusion: Idiopathic granulomatous hypophysitis is a very rare form of inflammatory pituitary disease. Fewer than 35 cases of biopsy-proven idiopathic granulomatous hypophysitis have been reported in medical literature. This is only the third case of biopsy-proven idiopathic granulomatous hypophysitis reported from India.
Paragangliomas are extremely rare chromaffin cell tumors arising from neural crest cells. Extra-adrenal paragangliomas originate from paravertebral and para-aortic paragangliomas distributed from the skull base to the pelvic floor. Here, we report a 57-year-old woman who presented with abdominal pain. Computed tomography revealed a solid mass at the renal hilum. The extent of disease was evaluated with 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET). Increased uptake of 18F-FDG was observed in the mass. The patient underwent diagnostic laparotomy, but the tumor was unresectable due to its close relationship with vascular structures. Pathologic examination confirmed that the tumor was a benign paraganglioma. To our knowledge, this location is extremely rare, and there are limited data reporting the value of PET scanning in the diagnosis of paragangliomas.
Malpighi supplied the final link in understanding the circulation of the blood. Galen described the 4 chambers of the heart and the connecting valves. He believed that arterial blood and venous blood communicated via pores in the interventricular system. Other anatomists, in particular Servetus and Colombo, described the pulmonary circulation in anatomic terms, but how the system functioned still remained a mystery. Fabricius of Aquapendente discovered the venous valves, allowing blood to flow only in the direction of the heart, and William Harvey put it all together in De Motu Cordis. He described the circulation as efferent from the left side of the heart, afferent into the right side of the heart, the 2 sides communicating through the pulmonary or minor circulation. It was still uncertain, however, how arterial blood made its transit into the venous system, a question conveniently ignored by Harvey. Malpighi squared the circle with his histological description of capillaries in frog and tortoise lungs and in the toad bladder. He observed the transit of "red globules" from artery to vein in in vivo preparations. He founded the science of microscopic anatomy, and is generally thought of as the "father of histology." Malpighi was born in Crevalcore, near Bologna Italy, on March 10, 1628. He was raised on a farm. He entered the University of Bologna at 17 years of age, but was forced to abandon his studies for more than 2 years to settle family affairs when his father, mother, and paternal grandmother all died within months of each other. He was granted doctorates in medicine and in philosophy in 1653. Upon graduation, he applied for a position as lecturer at Bologna, but it was 3 years before the post was awarded. He became a lecturer in logic. Contemporaneously, he was offered the first chair in Theoretical Medicine at the University of Pisa, which he accepted. He remained in Pisa for 3 years. It was in Pisa that Malpighi met and befriended Giovanni Borelli, a mathematician and polymath interested in animal movement among other more abstract things. Borelli exerted a powerful effect on Malpighi's scientific outlook and became a mentor for, and collaborator with Malpighi for the remainder of his life. After 3 years in Pisa, Malpighi returned to Bologna, claiming family pressures and poor health as the reasons. Three years later, on the recommendation of Borelli, he was again offered a professorship at another university, Messina. Again, Malpighi took the job and was appointed as a Professor Primus in Medicine. He remained there for 4 years and then returned to Bologna for the last time. He remained there for the next 25 years until, in 1691, in failing health, he was appointed as the personal physician to Pope Innocent XII. He died of a stroke in Rome on September 30, 1694. During his student age at Bologna, Malpighi was one of a few select students invited to attend private dissections and vivisections by Bartolomeo Massari, University Professor, and leading anatomist of his time. In 1654, Malpighi married Francesca Massari, the younger sister of the great anatomist. She died a year later, but Malpighi's life as an anatomist was entrained. Malpighi's first article appeared in 1661. It was published as 2 letters to his friend Borelli, "De pulmonibus." In this landmark article, Malpighi described the anatomy of the frog lung, bronchioles, alveoli, and the pulmonary capillary bed. In these capillaries, he could see, in vivo, "red globules" moving from arterioles to venules. The capillary bed was the final concept required to solidify the concept of the circulation of the blood. This and other articles were noticed by Henry Oldenburg, Secretary of the Royal Society of England. Oldenburg asked if Malpighi would correspond with him, and Malpighi became the first Italian fellow of the Royal Society. From this time forward, most of his discoveries were published in the proceedings of the Royal Society. He studied the development of the chicken embryo. He was convinced that he could see the form of the chick in unfertilized eggs. This became an important force in the "predelineation" movement. Of course, it was one of Malpighi's scientific errors. Malpighi's study of the liver, spleen, and kidney convinced him that organs are composed of glandular structures, corpuscles that, in aggregate, constitute the organ. He described the renal corpuscle (nephron), the splenic corpuscle (lymphoid centers), and the hepatic secretory unit. He studied insects and described the trachea through which insects breathe. He made a comprehensive study of the silkworm (De Bombyce). He studied the clotting of blood (de polypo cordis). He was the first person to describe the erythrocyte. He studied neuroanatomy and concluded that the brain is an endocrine organ. He studied plants and described the annular rings and deduced their function. The great Swedish botanist, Linnaeus named a genus of plants after Malpighi, the Malpighiaceae. The last decade of Malpighi's life was accompanied by challenge and criticism as often the case for scientific pioneers. Pope Innocent XII intervened and invited him to Rome in 1691 as papal archiater (first physician) to the Pope. He was further honored by election to the College of Doctors in Medicine and with a teaching appointment in the Papal Medical School. He died September 30, 1694. He is buried in the church of Santi Gregorio e Siro in Bologna. The inscription on the marble tablet over his tomb says, "Summum Ingenium, Integerrimam Vitam, Fortem Strenuamque Mentem, Audacem Salutaris Artis Amorem," (great genius, honest life, strong and tough mind, audacious love for the medical profession).FIGURE 1.: Marcello Malpighi.
Cerebral spinal fluid (CSF) rhinorrhea immediately after the initiation of cabergoline in prolactinoma patients is an uncommon complication that could lead to serious comorbidities and management difficulties. We present a case of a woman with multiple endocrine neoplasia type 1 syndrome and a recurrent macroprolactinoma, who developed CSF rhinorrhea and pneumocephalus after 3 doses of 0.5 mg cabergoline. The patient was treated for sinusitis after complaining of increasing headache. Imaging revealed a large pituitary tumor, skull base erosion, and pneumocephalus. Skull-base defect repair and subsequent transsphenoidal tumor debulking was performed. Prolactin continued to increase postoperatively, and the dopamine agonist (DA) was changed to bromocriptine, with no further CSF leak during 18 months of follow-up.We recommend urgent surgical repair as the treatment of choice for CSF leak following DA treatment. Concurrent surgical tumor debulking should be preformed if possible. Retreatment with DA is a safe option in most cases. To our knowledge, CSF rhinorrhea following cabergoline therapy has not been described in the multiple endocrine neoplasia type 1 syndrome.
The type B insulin-resistance syndrome is a rare autoimmune disease in which anti-insulin-receptor antibodies are formed. It generally affects young female patients with a history of other autoimmune diseases such as systemic lupus erythematosus. Difficult-to-control diabetes with alternating episodes of hyperglycemia and hypoglycemia suggest that the anti-insulin-receptor antibody is capable of both blocking insulin binding to its receptor and mimicking insulin action.The case of a man with preexisting diabetes and hypertension who developed liver cirrhosis is described. During hospitalization, the patient developed severe hyperglycemia, unresponsive to all available therapies, including up to 16,000 U/d of regular intravenous insulin without adequate control. A liver biopsy confirmed alpha-1-antitrypsin deficiency. Type B insulin-resistance was diagnosed concurrently. Treatment with cyclophosphamide was initiated, bringing about the characteristic presentation of the disease, with alternating episodes of hyperglycemia and hypoglycemia. When intravenous insulinotherapy was discontinued, the patient died of diabetic ketoacidosis refractory to emergency measures. This is the first described case correlating type B insulin-resistance syndrome and alpha-1-antitrypsin deficiency.
Objective: To describe a case of postmenopausal hyperandrogenemia in which a small ovarian tumor was ruled out by a positive metformin suppression test.Methods: We present the clinical, laboratory, and pathologic findings and the response to metformin.Results: A 52-year-old obese, postmenopausal, insulin resistant, female presented with hyperandrogenemia. With metformin therapy the testosterone level dropped by 76.9% and almost normalized. The positive result of the metformin suppression test was consistent with the diagnosis of postmenopause ovarian stromal hyperplasia, which was confirmed following bilateral oophorectomy.Conclusion: This case illustrates that in postmenopausal females with hyperandrogenemia the metformin suppression test may be helpful in eliminating a small ovarian tumor as a cause.
Objective: To present an unusual case of high bone mass (HBM) in a patient subsequently diagnosed with metastatic breast cancer.Methods: We describe the clinical presentation of our case and discuss its management.Results: A 41-year-old woman with pancytopenia was referred for HBM. Initial evaluations for malignancy, osteopetrosis II, mastocytosis, hepatitis C, and fluorosis were negative including normal whole body bone scan, mammogram, and 2 iliac crest bone marrow biopsies. Three months after initial presentation, she was hospitalized for abdominal pain, nausea, and vomiting. A CT scan of the abdomen and pelvis revealed diffuse bowel wall thickening and endoscopy showed friable mucosa throughout the GI tract. Pathology showed metastatic lobular breast carcinoma. The patient was treated with chemotherapy and had good responses of tumor markers, GI symptoms, and bone marrow function.Conclusion: Clinicians should be aware of the possibility of occult malignancy as a cause of HBM, even in the absence of the overt findings suggestive of metastatic bone disease.
This study evaluates the effect of L-thyroxin therapy on euthyroid nodular disease. The efficacy of treatment was evaluated by ultrasonography in 62 patients with benign euthyroid nodular goiter. Patients have been subdivided in 2 groups. About 35 patients were treated for 1 year with suppressive doses of thyroxine (study group) and 27 were followed without therapy. After L-thyroxin suppressive treatment, no significant difference was observed in both right and left thyroid lobe volume and dominant nodule volume. Only left thyroid volume significantly increased in control group. In our study, there was no significant effect on nodule volume with L-thyroxin treatment. Only left thyroid volume significantly increased in control (without treatment) group. Thus, the potential risks of long-term L-thyroxine therapy outweigh the potential benefits for most patients.
Thyroid nodules constitute the main indication for fine-needle aspiration biopsy (FNAB). The nodules that are diagnosed as microfollicular lesion by FNAB are usually excised because of the low but real probability that the nodule is malignant. In this study, the authors retrospectively assess the clinical factors that can be used to distinguish malignant versus benign nodules in patients with a FNAB specimen from microfollicular lesions in multinodular goiter patients.FNABs of thyroid nodules with a microfollicular structure were included in the study. All cases were reviewed to assess the following clinical features: sex, thyroid functional status, age, and nodule size.A total of 41 patients with microfollicular lesion in the FNAB specimen underwent total thyroidectomy. Final pathology result revealed 6 malignant nodules (14.6%) and 35 (85.4%) benign nodules. There were no differences in age, sex, functional status, and nodule size between patients with benign versus malignant disease.Clinical factors (sex, age, nodule size, etc) are not helpful for predicting malignancy in thyroid nodules with a microfollicular structure by FNAB.
