WEBVTT 1 00:00:00.840 --> 00:00:03.270 Hi, everyone, and welcome to today's lecture 2 00:00:03.270 --> 00:00:06.420 on the Epidemiology of Adrenal Cancer. 3 00:00:06.420 --> 00:00:08.310 In this lecture, we have several goals. 4 00:00:08.310 --> 00:00:09.900 We'll begin by reviewing the anatomy 5 00:00:09.900 --> 00:00:12.300 and function of adrenal glands. 6 00:00:12.300 --> 00:00:14.010 Then we'll differentiate tumors 7 00:00:14.010 --> 00:00:16.320 of the adrenal cortex and medulla. 8 00:00:16.320 --> 00:00:17.970 Next, we'll discuss characteristics 9 00:00:17.970 --> 00:00:21.600 of adrenal cortical tumors and risk factors for those tumors 10 00:00:21.600 --> 00:00:25.890 and then look at characteristics of adrenal medulla tumors 11 00:00:25.890 --> 00:00:28.443 and look at some genetic syndromes. 12 00:00:29.760 --> 00:00:33.180 So, to begin with, let's give a brief overview 13 00:00:33.180 --> 00:00:35.100 of the anatomy of the adrenal glands. 14 00:00:35.100 --> 00:00:38.280 So the adrenal glands are bilateral, triangular structures 15 00:00:38.280 --> 00:00:41.550 positioned above and slightly behind the kidneys. 16 00:00:41.550 --> 00:00:44.010 Each gland consists of the adrenal cortex 17 00:00:44.010 --> 00:00:45.870 and the adrenal medulla. 18 00:00:45.870 --> 00:00:47.970 The adrenal cortex consists of zones 19 00:00:47.970 --> 00:00:49.620 of cuboidal epithelial cells 20 00:00:49.620 --> 00:00:53.130 that actively synthesize and secrete steroid hormones, 21 00:00:53.130 --> 00:00:57.423 and all steroid hormones are synthesized from cholesterol. 22 00:00:58.380 --> 00:01:02.100 Adrenal steroids include corticosteroids like cortisol 23 00:01:02.100 --> 00:01:04.950 that regulate the metabolism of protein, fat, 24 00:01:04.950 --> 00:01:09.950 and carbohydrates and mineral corticoids like aldosterone 25 00:01:10.890 --> 00:01:13.440 that regulates salt and water balance. 26 00:01:13.440 --> 00:01:17.730 The adrenal cortex also synthesizes low levels of androgens 27 00:01:17.730 --> 00:01:20.070 and estrogens that help modulate masculine 28 00:01:20.070 --> 00:01:21.813 and feminine characteristics. 29 00:01:24.750 --> 00:01:27.240 Adrenal masses or adrenal tumors are often 30 00:01:27.240 --> 00:01:29.460 found incidentally during imaging studies 31 00:01:29.460 --> 00:01:31.200 for other conditions. 32 00:01:31.200 --> 00:01:33.870 Most adrenal masses are benign adenomas 33 00:01:33.870 --> 00:01:35.760 and only a small fraction, 34 00:01:35.760 --> 00:01:39.723 something around the 10%, prove to be malignant on biopsy. 35 00:01:41.160 --> 00:01:42.990 Definitive differentiation of benign 36 00:01:42.990 --> 00:01:45.750 from malignant adrenal tumors is often problematic 37 00:01:45.750 --> 00:01:48.900 and requires careful evaluation of structural, clinical, 38 00:01:48.900 --> 00:01:52.860 hormonal, cytologic and molecular features. 39 00:01:52.860 --> 00:01:55.980 Diagnostic symptoms of adrenal tumors are often 40 00:01:55.980 --> 00:01:58.500 related to hormonal imbalance due to hyper secretion 41 00:01:58.500 --> 00:02:02.520 of specific hormones by dysplastic and malignant cells. 42 00:02:02.520 --> 00:02:05.490 For example, Cushing's syndrome is the excessive production 43 00:02:05.490 --> 00:02:08.160 of cortisol, and that influences the body's, 44 00:02:08.160 --> 00:02:11.070 or cortisol influences the body's response to stress, 45 00:02:11.070 --> 00:02:13.833 metabolism of fat and protein and immune function. 46 00:02:14.790 --> 00:02:16.830 Another example is Conn's disease 47 00:02:16.830 --> 00:02:19.602 which is the excessive production of aldosterone 48 00:02:19.602 --> 00:02:22.020 which leads to increased salt retention, 49 00:02:22.020 --> 00:02:24.513 potassium depletion, and elevated blood pressure. 50 00:02:26.160 --> 00:02:28.350 The dominant clinical manifestation of tumors 51 00:02:28.350 --> 00:02:31.710 of the adrenal medulla, which is neuroblastoma 52 00:02:31.710 --> 00:02:36.710 in children and pheochromocytoma adults, is hypertension. 53 00:02:37.410 --> 00:02:39.960 This is due to the excessive production 54 00:02:39.960 --> 00:02:44.493 of epinephrine and norepinephrine. 55 00:02:45.600 --> 00:02:47.700 Measurement of the levels of these hormones in blood 56 00:02:47.700 --> 00:02:50.250 and urine aid in the differential diagnosis 57 00:02:50.250 --> 00:02:51.843 of adrenal tumors. 58 00:02:53.370 --> 00:02:55.920 Malignant tumors that arise from the adrenal cortex 59 00:02:55.920 --> 00:02:58.800 are called adrenal cortico carcinomas. 60 00:02:58.800 --> 00:03:01.830 Adrenal tumors that secrete adrenal steroids are classified 61 00:03:01.830 --> 00:03:05.190 as functional, whereas non-secreting tumors are classified 62 00:03:05.190 --> 00:03:07.110 as non-functional. 63 00:03:07.110 --> 00:03:11.100 Most or 90% of adrenal cortical carcinomas secrete steroids 64 00:03:11.100 --> 00:03:12.550 and are therefore functional. 65 00:03:14.490 --> 00:03:17.280 Adrenal cortical carcinomas are rare and accurate data 66 00:03:17.280 --> 00:03:19.950 on their incidents and mortality is lacking. 67 00:03:19.950 --> 00:03:23.880 A review of 1,891 cases identified in the English literature 68 00:03:23.880 --> 00:03:28.880 between 1952 and 1992 found that 58.6% of cases were female 69 00:03:29.970 --> 00:03:32.100 with a first peak of onset in childhood 70 00:03:32.100 --> 00:03:35.130 and a second peak during the fifth decade of life. 71 00:03:35.130 --> 00:03:38.280 We see that in this figure on the slide 72 00:03:38.280 --> 00:03:41.250 with the slightly elevated bar in the birth to 10 age range 73 00:03:41.250 --> 00:03:45.240 and the high bar between 51 and 60 years. 74 00:03:45.240 --> 00:03:47.790 In the US, the annual incidents estimated 75 00:03:47.790 --> 00:03:50.400 from surveillance epidemiology and end results data 76 00:03:50.400 --> 00:03:54.300 or SEER data is less than one case per million. 77 00:03:54.300 --> 00:03:57.330 The age or diagnosis ranges from one to 91 years of age 78 00:03:57.330 --> 00:03:59.760 with a small early peak during childhood 79 00:03:59.760 --> 00:04:01.243 and as previously mentioned, 80 00:04:01.243 --> 00:04:04.263 the larger peak in the fifth decade of life. 81 00:04:05.610 --> 00:04:09.540 So in 2020, it's difficult to find accurate incidents 82 00:04:09.540 --> 00:04:11.250 and mortality data. 83 00:04:11.250 --> 00:04:14.310 Though the data that is available state 84 00:04:14.310 --> 00:04:17.280 that adrenal cancer is very rare. 85 00:04:17.280 --> 00:04:20.280 Overall, in the US incidence is estimated to be 86 00:04:20.280 --> 00:04:24.870 about one per 1 million or 1.02 per 1 million overall. 87 00:04:24.870 --> 00:04:26.310 To give you an idea 88 00:04:26.310 --> 00:04:29.130 of how rarely this form of cancer appears, 89 00:04:29.130 --> 00:04:34.130 there were only 2014 cases between 1973 and 2014. 90 00:04:34.470 --> 00:04:38.250 However, it typically has a highest mortality rate 91 00:04:38.250 --> 00:04:41.073 due to the typical late stage presentation. 92 00:04:43.050 --> 00:04:46.110 There's several risk factors for adrenal cortical carcinomas 93 00:04:46.110 --> 00:04:47.850 including tobacco smoking, 94 00:04:47.850 --> 00:04:50.193 and a number of genetic syndromes. 95 00:04:51.720 --> 00:04:53.160 The two principle tumors 96 00:04:53.160 --> 00:04:55.650 of the adrenal medulla are neuroblastoma 97 00:04:55.650 --> 00:04:57.903 and pheochromocytoma. 98 00:04:58.920 --> 00:05:01.530 Both tumors arise from neuroendocrine tissues 99 00:05:01.530 --> 00:05:06.360 of the adrenal medulla, and thus may secrete catecholamines 100 00:05:06.360 --> 00:05:08.660 that influence the sympathetic nervous system. 101 00:05:09.720 --> 00:05:12.780 There are distinct differences in the clinical 102 00:05:12.780 --> 00:05:15.402 and pathological features of these tumors 103 00:05:15.402 --> 00:05:18.840 and neuroblastomas are diagnosed primarily in children 104 00:05:18.840 --> 00:05:22.503 while pheochromocytomas are diagnosed primarily in adults. 105 00:05:25.080 --> 00:05:30.080 Risk factors for neuroblastomas include certain gestational 106 00:05:30.690 --> 00:05:33.660 and maternal exposures, including opiates, 107 00:05:33.660 --> 00:05:36.093 folate deficiency, and gestational diabetes. 108 00:05:38.760 --> 00:05:42.390 There's also several genetic syndromes that play a role 109 00:05:42.390 --> 00:05:44.160 in neuroblastoma development. 110 00:05:44.160 --> 00:05:47.310 These include Turner syndrome, Hirschsprung's disease 111 00:05:47.310 --> 00:05:49.950 and Neurofibromatosis Type 1. 112 00:05:49.950 --> 00:05:53.612 You can read more about all of these syndromes 113 00:05:53.612 --> 00:05:55.173 in your textbook. 114 00:05:57.600 --> 00:05:59.580 The second main class of tumors 115 00:05:59.580 --> 00:06:03.210 which affects primarily adults or pheochromocytomas 116 00:06:03.210 --> 00:06:05.180 arise from chromaffin cells of the medulla 117 00:06:05.180 --> 00:06:08.400 of the adrenal gland or other anatomic sites. 118 00:06:08.400 --> 00:06:11.280 These are typically benign and most often detected 119 00:06:11.280 --> 00:06:14.190 in adults from 20 to 50 years of age. 120 00:06:14.190 --> 00:06:16.500 They cause marked elevations in blood pressure 121 00:06:16.500 --> 00:06:21.500 or hypertension, and over 90% have no metastatic potential. 122 00:06:22.320 --> 00:06:24.603 These are typically curable by excision. 123 00:06:26.790 --> 00:06:28.770 A significant fraction of cases, 124 00:06:28.770 --> 00:06:31.350 perhaps 30%, occur in familial settings 125 00:06:31.350 --> 00:06:34.230 with multi-generational inheritance patterns. 126 00:06:34.230 --> 00:06:35.063 The most common 127 00:06:35.063 --> 00:06:39.180 of these hereditary conditions is von Hippel-Lindau disease 128 00:06:39.180 --> 00:06:44.180 or VHL and the multiple endocrine neoplasia or MEN syndrome. 129 00:06:44.250 --> 00:06:47.647 The first is a rare autosomal dominant genetic condition 130 00:06:47.647 --> 00:06:49.650 tied to a germ line mutation 131 00:06:49.650 --> 00:06:53.010 in the von Hippel-Lindau tumor suppressor gene 132 00:06:53.010 --> 00:06:54.963 on the short arm of chromosome three. 133 00:06:56.550 --> 00:06:58.350 In contrast, the MEN 134 00:06:58.350 --> 00:07:03.350 and Sipple syndromes are a heritable syndrome 135 00:07:04.980 --> 00:07:09.980 caused by mutations of the M, E, N, I, N or MENIN gene 136 00:07:10.080 --> 00:07:11.340 which is the tumor suppressor gene 137 00:07:11.340 --> 00:07:13.653 located on chromosome 11.