内分泌英文病历讨论(学生版)

Case Discussion

A 35-year-old pregnant woman (gravida 2胎次, para 1) was admitted to this hospital at 19 weeks and 6 days of gestation怀孕期because of the recent onset of hypertension and diabetes.

Three weeks before admission, at a routine prenatal visit, her blood pressure was 150/100(150 over 100) mm Hg(millimeters hydragyrim). On the same day she saw her primary care physician, who recorded a blood pressure of 172/102 mm Hg. The results of a physical examination were normal. Urinalysis showed glucose (4+). The results of other laboratory tests are shown in Table 1. The next day, the blood pressure was 180/100 mm Hg. The blood glucose level 1 hour after the oral administration of glucose (50 g) was 346 mg per deciliter[?desili:t?] 分升(19.2 mmol per liter). Treatment with labetalol拉贝洛尔, glyburide格列本脲（优降糖）, and potassium [p??t?si?m]钾supplements was initiated. The results of fetal ultrasound examination were normal for the gestational age of the fetus [?fit?s]. Three weeks later, despite increasing doses of labetalol, the patient's blood pressure remained in the range of 180/110 mm Hg and her fasting blood glucose level ranged between 140 and 180 mg per deciliter (7.8 and 10.0 mmol per liter); the patient was admitted to the hospital.

The patient had gained 6.8 kg in weight during the pregnancy. She had recently had polyuria and polydipsia and increased facial puffiness虚胖; her complexion面色was chronically ruddy红润. She did not have headaches, proximal muscle weakness, bruising挤压伤, flushing激动脸红, abdominal pain, edema, palpitations心悸, diaphoresis [,dai?f?'ri:sis]发汗(sweat), edema, or changes in vision. Her menses had been regular before pregnancy, and she had had no difficulty conceiving怀胎with either this pregnancy or a pregnancy 3 years earlier, during which she had mild, diet-controlled gestational diabetes. She had been mildly overweight, with a body-mass index （BMI）(the weight in kilograms divided by the square of the height in meters) of approximately 25 for several years. She did not smoke, drink alcohol, or use illicit [?'l?s?t]非法的drugs. She was married, with a 2-year-old daughter. Her mother and maternal [m??t?:nl]母亲方面的grandmother had type 2 diabetes mellitus, and many family members had hypertension.

Q1: What’s the possible cause of the patient? Give 3 or more diseases for hypertension during pregnancy.

1.preeclampsia or eclampsia

2.chronic hypertension probable diagnosis

3.preeclampsia or eclampsia superimposed on chronic hypertension

4.gestational hypertension

When I saw this patient during her first admission, she had marked hypertension, poorly controlled diabetes mellitus, and hypokalemia. The four hypertensive disorders that are recognized during pregnancy are preeclampsia[?pri??kl?mpsi?]先兆子痫or eclampsia [ek?l?mpsi?] 子痫惊厥, chronic hypertension(including "essential" hypertension and secondary hypertension), preeclampsia or eclampsia superimposed[?sju:p?rim?p?uzd]on chronic hypertension, and gestational hypertension. Although this patient had proteinuria, it was not severe enough to warrant正当理由a diagnosis of preeclampsia; in addition, the onset of preeclampsia would be unlikely this early in the pregnancy. Gestational hypertension would also be unlikely this early in pregnancy. Thus, I was left with a probable diagnosis of chronic hypertension.

In a patient with newly diagnosed chronic hypertension, the major question is whether it is essential hypertension or associated with another condition. A pregnant patient with chronic hypertension is at increased risk for superimposed preeclampsia, intrauterine子宫

内的growth restriction(grow slowly), abruption分裂placentae [pl??sent?]胎盘(胎盘早剥正常20week to birth), premature birth, and perinatal [?peri?neitl]围产期death. Efforts to control blood pressure with labetalol or methyldopa甲基多巴to reduce the incidence of preeclampsia and its associated perinatal morbidity发病率have been disappointing; thus, a search for a secondary cause in a case such as this is mandatory必要的强制的. In this patient, the presence of hypokalemia increased my suspicion that the problem was secondary hypertension.

Q2: Did the patient have preexisting, undiagnosed diabetes? Why?

Yes

The glycated hemoglobin value of 8.2% at 16 weeks and 6 days' gestation led me to suspect that she had had hyperglycemia for some time before her pregnancy began.

The broad definition of gestational diabetes includes the coincidental development of type 1 during pregnancy as well as the presence of preexisting, undiagnosed type 2.

Diabetes in Pregnancy

This patient also had carbohydrate intolerance, with glycosuria at 16 weeks and 6 days' gestation, as well as gestational diabetes (defined as carbohydrate intolerance of any degree of severity, with an onset or first recognition during pregnancy). The glycated hemoglobin value of 8.2% at 16 weeks and 6 days' gestation led me to suspect that she had had hyperglycemia for some time before her pregnancy began. The broad definition of gestational diabetes includes the coincidental巧合的development of type 1 during pregnancy as well as the presence of preexisting, undiagnosed type 2. The vast majority of patients who receive a diagnosis of gestational diabetes have a relatively mild degree of carbohydrate intolerance that develops late in pregnancy and is associated with the insulin resistance of pregnancy. It seemed fairly clear to me that this woman had preexisting, undiagnosed type 2 diabetes. The results of additional laboratory tests (Table 2) led me to suspect that she had Cushing's syndrome and to request a consultation with an endocrinologist.

Q3: What is keypoint in the next physical examination?

BMI and weight gain

blood pressure and pulse

edema (face orbital peripheral)

extraocular movements and visual fields

thyroid

supraclavicular or dorsal adipose tissue, hirsutism, bruising痤疮

abdomen striae

Proximal muscle strength and reflexes

Cushing's Syndrome in Pregnancy

In a case that is suggestive of Cushing's syndrome, the goals are to confirm the presence of a pathologic excess of endogenous cortisol, to determine its source, and to remove the source to prevent illness and death. Both the diagnosis and management in this case were further complicated by the patient's pregnancy. The diagnosis of Cushing's syndrome in pregnancy is confounded by the normal hormonal and biochemical changes of pregnancy; the management is confounded by the profoundly极度的leterious effect of hypercortisolemia on both mother and fetus, the side effects of medications, and the technical problems involved in undertaking surgical resection. The complications of pregnancy for women with Cushing's syndrome include hypertension, diabetes, preeclampsia, and infection. Fetal complications include prematurity and intrauterine growth retardation延迟.

This patient had no signs or symptoms of Cushing's syndrome before pregnancy. Consideration of the diagnosis of Cushing's syndrome is typically based on clinical features. However, many features of this disease are similar to those of normal pregnancy, including weight gain, amenorrhea[ei?men??ri:?]无月经, striae条纹, fatigue[f??tiɡ]劳累, back pain, mood changes, and plethora [?pleθ?r?]过量过剩.In this patient, clinically significant hypertension and abnormal glucose tolerance were present; although these findings are common in Cushing's syndrome, they are nonspecific.Objective signs favoring a diagnosis of Cushing's syndrome — such as weakness, particularly proximal weakness, spontaneous [spɑn?teni?s]自然发生的ecchymoses[eki?m?usis]瘀斑, and wide striae — were

not seen in this case, probably because the development of hypercortisolemia had been rapid.The single finding that appropriately prompted an evaluation of this patient for Cushing's syndrome was unexplained hypokalemia.

On physical examination, the patient's weight was 80 kg and height 170 cm, with a body-mass index of 28. The blood pressure was 180/100 mmHg, and the pulse was 88 beats per minute; other vital signs were normal. Her face was slightly rounded, there was mild per orbital眼窝的edema, and her facial complexion was ruddy. Extraocular [?ekstr???kjul?]眼外的movements and visual fields were intact未受损伤. The thyroid was normal in size, with no palpable nodules. There was no increase in supraclavicular锁骨上的or dorsal adipose脂肪tissue, hirsutism多毛症, or evidence of bruising擦伤. The abdomen was gravid怀孕的, nontender, and without striae. Proximal muscle strength and reflexes were normal. There was no peripheral edema.

Q4: Then what is your diagnosis? Why?

chronic hypertension

gestational diabetes（type 2 diabetes）

hypokalemia

Cushing’s syndrome?

Q5: Are there any other examinations we should take? Why?

Confirmation of a pathologic excess of cortisol is based on one or more of three methods: assessment of total cortisol production over a 24-hour period with a determination of 24-hour urinary free cortisol

documentation of the loss of normal diurnal variation in cortisol secretion on the basis of a late-night salivary cortisol measurement

documentation of the loss of feedback inhibition of cortisol on the hypothalamic–pituitary–adrenal axis with dexamethasone suppression testing

To rule out an aldosterone-secreting tumor as a cause of hypokalemia

aldosterone level and elevated plasma renin activity

to find the location of the lesion(adrenal , pituitary or ectopic)

magnetic resonance imaging (MRI)

to determine if the Cushing's syndrome caused by excess corticotropin or not

an undetectable corticotropin level or a 9 a.m. level below 10 pg per milliliter with a two-site immunoradiometric assay

Q6: What is your prescription for this patient?

Labetalol(until the blood pressure became normal)

硝苯地平

insulin and potassium supplementation

In this patient, rapidly escalating hypertension and insulin-requiring diabetes made surgical cure an immediate goal. If surgery cannot be performed in a case such as this, the use of interim medical therapy to block cortisol production should be considered. In this case, metyrapone美替拉酮, a drug that blocks the conversion of 11-deoxycortisol脱氧可的松to cortisol, was used briefly while surgery was being scheduled. The use of metyrapone during pregnancy has been reported in a few cases15,16,17,18; however, definitive surgery usually should not be delayed until the cortisol level is normalized. Other drugs more commonly used to treat hypercortisolemia, such as ketoconazole酮康唑, cross the placenta, inhibit progesterone production, and may be both teratogenic [?ter?t?u?d?enik]产生畸形and associated with fetal loss.

One week later, the patient was seen in the neuroendocrine clinic. The results of additional laboratory tests were showed in Table 2. A repeated 24-hour urinary cortisol measurement showed that the level was 1805 μg.

Q7:How to confirm the presence of a pathologic excess of cortisol？

Confirmation of a pathologic excess of cortisol is based on one or more of three methods: assessment of total cortisol production over a 24-hour period with a determination of 24-hour urinary free cortisol, documentation of the loss of normal diurnal variation in cortisol secretion on the basis of a late-night salivary cortisol measurement, and documentation of the loss of feedback

inhibition of cortisol on the hypothalamic–pituitary–adrenal axis with dexamethasone suppression testing. The biochemical diagnosis of hypercortisolemia in pregnancy is complicated by two factors.

Detecting Pathologically Excessive Cortisol Production

Confirmation of a pathologic excess of cortisol is based on one or more of three methods: assessment of total cortisol production over a 24-hour period with a determination of 24-hour urinary free cortisol, documentation of the loss of normal diurnal variation in cortisol secretion on the basis of a late-night salivary cortisol measurement, and documentation of the loss of feedback inhibition of cortisol on the hypothalamic–pituitary–adrenal axis with dexamethasone suppression testing.The biochemical diagnosis of hypercortisolemia in pregnancy is complicated by two factors. First, cortisol production rates markedly increase during pregnancy, so that urinary free cortisol levels in the second and third trimesters may overlap with levels seen in Cushing's syndrome. Second, levels of corticotropin促肾上腺皮质激素rise despite increasing cortisol levels, which is consistent with the occurrence of decreased feedback on corticotropin secretion. Therefore, unless cortisol levels are markedly elevated, the results of these tests may be difficult to interpret.

In healthy people, cortisol secretion peaks in early morning and reaches a nadir as midnight approaches; the difference in cortisol secretion between such people and those with Cushing's syndrome is maximal at approximately 11 p.m.4 However,although this difference provides an excellent screening test for Cushing's syndrome, normal late-night salivary cortisol levels are not well established during pregnancy.

Low-dose dexamethasone suppression testing can be used to diagnose Cushing's syndrome despite the occurrence of false negative results. During pregnancy, however, false positive results can occur. Possible reasons for false positive results include an estrogen-induced elevation in the cortisol-binding globulin; the impaired suppressibility of the hypothalamic–pituitary–adrenal axis; placental production of corticotropin and corticotropin-releasing hormone, which is not regulated by negative feedback control; tissue refractoriness to glucocorticoids; and possible antiglucocorticoid effects of progesterone.4g 2天每天4次

In this case, urinary free cortisol levels that were more than 1000 μg above the upper limit of the normal range during two 24-hour periods in the absence of glucocorticoid therapy clearly established the diagnosis of Cushing's syndrome. The hypokalemia reflected the magnitude of this excess cortisol. The normal aldosterone level and elevated plasma renin activity were consistent with pregnancy, ruling out an aldosterone-secreting tumor as a cause of hypokalemia.

Q8: How to determine the source of a pathologic excess of cortisol?

Corticotropin-independent Cushing's syndrome is due to an adrenal lesion, whereas the corticotropin-dependent form of the disease can be traced to either a pituitary垂体的or an ectopic source.

In Cushing's syndrome caused by excess corticotropin from any source, corticotropin levels are typically in the normal range — which is inappropriate given the level of cortisol — or they are elevated. In corticotropin-independent Cushing's syndrome, corticotropin levels should be suppressed.

In the setting of hypercortisolemia, an undetectable corticotropin level or a 9 a.m. level below 10 pg per milliliter (2 pmol per liter) with a two-site immunoradiometric免疫放射测定assay is considered to be suggestive of corticotropin-independent Cushing's syndrome.

Determining the Cause of Excess Cortisol Production

Once pathologic hypercortisolemia has been identified, the next step is to determine whether the hormone excess is corticotropin-dependent. Corticotropin-independent Cushing's syndrome is due to an adrenal lesion, whereas the corticotropin-dependent form of the disease can be traced to either a pituitary垂体的or an ectopic source.The most common cause of endogenous Cushing's syndrome is overproduction of corticotropin by a benign pituitary corticotropic tumor.The vast majority of such tumors are microadenomas (<1 cm in diameter); approximately one third are too small to be visualized on sensitive high-resolution magnetic resonance imaging (MRI). Ectopic 易位的Cushing's syndrome is caused by a neoplasm outside of the pituitary gland that produces corticotropin or, in rare cases, corticotropin-releasing hormone. Many tumors have been reported to cause ectopic Cushing's syndrome,

but the most common are pulmonary in origin, ranging from carcinoid tumors to bronchogenic carcinomas.

In Cushing's syndrome caused by excess corticotropin from any source, corticotropin levels are typically in the normal range —which is inappropriate given the level of cortisol — or they are elevated. In corticotropin-independent Cushing's syndrome, corticotropin levels should be suppressed. In the setting of hypercortisolemia, an undetectable corticotropin level or a 9 a.m. level below 10 pg per milliliter (2 pmol per liter) with a two-site immunoradiometric免疫放射测定assay is considered to be suggestive of corticotropin-independent Cushing's syndrome.However, because corticotropin levels may be higher in pregnant women than in nonpregnant women, this measure may be misleading. Therefore, unless corticotropin levels are lower than normal, a corticotropin-dependent tumor may be erroneously diagnosed. In this case, the corticotropin level of 3 pg per milliliter (0.6 nmol per liter) in the setting of profound hypercortisolemia was strongly suggestive of an adrenal source of Cushing's syndrome, and it led us to order an adrenal MRI without the administration of contrast material.

Q9: What is the most common cause of endogenous Cushing's syndrome?

The most common cause of endogenous Cushing's syndrome is overproduction of corticotropin by a benign pituitary corticotropic tumor.

Ectopic 易位的Cushing's syndrome is caused by a neoplasm outside of the pituitary gland that produces corticotropin or, in rare cases, corticotropin-releasing hormone. Many tumors have been reported to cause ectopic Cushing's syndrome, but the most common are pulmonary in origin, ranging from carcinoid tumors to bronchogenic carcinomas.

The abdominal MRI scan reveals a left adrenal mass, 5.4 by 4.3 by 3.8 cm, with well-defined borders, that is relatively homogeneous同性质in signal intensity.

Figure 1. Axial MRI of the Left Adrenal Gland.

Panel A shows a very well-circumscribed mass

(arrow) in the left adrenal gland with a low,

relatively homogeneous signal intensity on this

in-phase T^sub 1^-weighted image (echo time,

4.2 msec) and no evidence of local invasion. In

Panel B, the out-of-phase T^sub 1^-weighted

image (echo time, 2.1 msec) 反相位shows no

marked decrease in the signal intensity of the

mass (arrow), unlike a typical adenoma. In Panel

C, a T^sub 2^-weighted image shows that the

mass (arrow) has only intermediate中等signal

intensity, unlike a typical pheochromocytoma

[?fi:?kr?um?sai?t?um?]嗜铬细胞瘤. Thus, this

large, solid left adrenal mass has no specific or

characteristic features on MRI.

Q10: What is the final diagnosis now?

Cushing's syndrome due to adrenal cortical carcinoma.

An intraoperative外科手术进行时photograph (Panel A) shows the adrenal tumor (arrow) after mobilization and before removal. The tumor was approximately 5 cm in diameter, was well circumscribed, and did not invade adjacent [??d?es?nt]毗邻的tissues. On microscopical examination, there was a trabecular小梁的and nested pattern (Panel B, hematoxylin and eosin). In addition, two types of tumor cells are present: one type has abundant, lipid-rich, clear cytoplasm, with small nuclei and no mitotic cells, resembling the cells seen in the zona fasciculata of the normal adrenal cortex (Panel B); the other type has abundant eosinophilic cytoplasm and more nuclear atypia, with occasional mitotic cells (Panel C, hematoxylin and eosin).

In summary, this patient had a large, solid left adrenal mass, without evidence of invasion, but with no specific or characteristic features on MRI studies.

Q11: What is your prescription for this patient?

Laparoscopic adrenalectomy and glucocorticoid replacement with dexamethasone等待ACTH水平恢复Labetalol(until the blood pressure became normal)

Prednisone(continued throughout the pregnancy)

insulin and potassium supplementation

Immediately after the MRI, the patient was readmitted to the hospital at 21 weeks' gestation. The blood pressure was 148/88 mm Hg. Metyrapone (250 mg three times daily) was administered, and the blood pressure gradually normalized. The insulin dose was increased to 112 U daily.

The patient was performed a laparoscopic adrenalectomy 6 days after admission.After the operation, glucocorticoid replacement with dexamethasone was begun. Postoperative tests showed complete suppression of the levels of 24-hour urinary cortisol and morning serum cortisol. The results of thyroid function tests normalized. During the next 10 days, the labetalol dose was tapered and discontinued, and blood pressure remained normal. Prednisone (5 mg twice daily) was continued throughout the pregnancy. The patient continued to require insulin and potassium supplementation.

Q12: Give a summary for the patient.